Gliatilin - instructions for use (adults and children), analogs, reviews

Gliatilin - instructions for use (adults and children), analogs, reviews

Gliatilin represents itself as a nootropic drug that improves human cognitive abilities (memory, attention and productivity of thought), as well as normalize cerebral circulation. Gliatilin is used in stroke, memory loss, lack of cerebral circulation (vascular encephalopathy) and dementia (senile, Alzheimer's, etc.).

Structure and Composition of Gliatilin

Currently Gliatilin available in two dosage forms:
1. Capsules for oral administration;
2. The solution in vials for intramuscular or intravenous administration.

Capsules colloquially often called pills, meaning dosage form intended for oral administration. Of course, the capsule - is not the same dosage form tablets, but on the everyday level to indicate the drug varieties for intake may well be used both names. It is necessary to remember that if a person says "Gliatilin pills," he is referring to a form for oral administration, ie the capsule.

Gliatilin capsules are available in packs of 14 pieces. The solution for intravenous and intramuscular injection is available in ampoules of 4 ml, which are packaged in cartons of 1 or 3 pieces. Gliatilin solution is a clear, colorless liquid with no odor. Shell gelatin capsules have an oval shape, colored in yellow. Inside the capsule is a viscous, colorless solution.

The active substance of Gliatilin capsules and Gliatilin injection is choline alfoscerate. The capsules have a dosage of 400 mg of the active substance and the solution - 250 mg / ml. That is, each capsule contains 400 mg of choline alfoscerate, and 1 ml of solution for injections - 250 mg. Accordingly, a full ampoule with 4 ml of solution contains 1000 mg of active substance (choline alfoscerate).

As an adjuvant injection comprises a sterile deionized distilled water. Capsules Gliatilin as auxiliary components include the following substances: Glycerine; Titanium dioxide; Gelatin; metahydroxide iron (III); Purified water; Sodium Propyl; Sorbitans; sodium ethyl parahydroxybenzoate; Ezitol.

Therapeutic action of Gliatilin

Gliatilin is a central cholinomimetic actions, that is, has an activating effect on the cholinergic receptors in the brain structures. According to the pharmacological action of the drug it is a nootropic and neuroprotective.
Once in the brain, Gliatilin decomposes with the release of choline and glycerophosphate. Choline is involved in the formation of acetylcholine - a substance which is the main mediator of nervous excitement. It is due to acetylcholine signal transmitted from one brain cell to another. In fact, the availability of sufficient quantities of acetylcholine defines high-speed exchange of information between the brain structures.

A glycerophosphate involved in the formation of phospholipids - substances constituting the cell membrane. Accordingly, a sufficient amount of phospholipids, cells have a strong membrane that protects them from the negative effects of environmental factors.
Thus, on the one hand, Gliatilin accelerates and improves the transmission of nerve impulses between brain cells, and on the other makes neurons more durable and resistant to adverse environmental factors (eg, hypoxia, etc.).

In addition, Gliatilin improves cerebral blood circulation, accelerates metabolism in brain cells and restores consciousness after traumatic injuries of various brain structures. When used in the acute period of craniocerebral trauma Gliatilin improves blood flow and electrical activity in the affected area, as well as promotes a more rapid disappearance of neurological symptoms and recovery of normal consciousness. Gliatilin also contributes to the rapid recovery and normalization of the structures damaged in the course of ischemic stroke brain.
Gliatilin also improves cognitive abilities (memory, attention and thinking) in people with mild to severe dementia, caused by disorders of cerebral circulation of various origins, such as atherosclerosis, cerebral blood vessels, circulatory encephalopathy, hypertension, Alzheimer's disease, etc.
All people (both healthy and suffering from disorders of mental activity) Gliatilin improves mood and emotional stability, stimulates thinking, relieves irritability and apathy.

Indications for Gliatilin
Gliatilin indicated for use under the following conditions and diseases:

• acute period of traumatic brain injury, in which mostly struck by the brain stem, and there is a corresponding symptoms (disturbance of consciousness, coma, etc.);
• Acute and rehabilitation period of ischemic stroke; The recovery period of hemorrhagic stroke;
• Degenerative and involution psycho-organic syndrome, manifested memory impairment, confusion, disorientation, decreased motivation, initiative and concentration;
• Chronic cerebrovascular insufficiency (encephalopathy);
• Violations of emotional stability and behavior, such as emotional lability, irritability, low interest in life, senile pseudo-melancholy;
• Dementia is caused by various reasons (Alzheimer's, senile, mixed forms);
• Alzheimer's disease;
• Huntington's Chorea;
• Cognitive disorders (disorders of mental function, memory and concentration in the elderly, as well as confusion, disorientation, decreased motivation and initiative).

Gliatilin - instructions for use
General provisions
Gliatilin capsules are taken orally and is used to treat chronic conditions for a long period of time. Gliatilin solution was administered intravenously or intramuscularly and used in the treatment of acute conditions in a relatively short period of time. Furthermore, severe disease gliatilin combined use of injection and in the form of capsules, i.e., first administered intravenously or intramuscularly solution, and then continue to receive treatment with the capsules inside.
Selecting the way to use gliatilin performed by a doctor depending on the severity of the disease and the patient's condition. Consider the scheme, rules of application and the dosage of solution and gliatilin capsules for the treatment of various conditions and diseases.

Application of Gliatilin capsulesThe capsules should be swallowed whole, not open, not revealing in other ways, and with a small amount of still water. It is better to take the capsules before meal.

If you want to take the capsules several times a day, you should divide the daily dosage into unequal parts so that in the morning to take a large part of the dose, and during the day - less. This is necessary to offset the possible stimulating effect of the drug, due to which you may have difficulty falling asleep, if we take it in the evening.

When chronic treatment immediately begin taking the capsules with 400 mg (1 capsule) in 2 - 3 times a day and continued for 3 - 6 months. In acute conditions initially carried gliatilin course of injections (administered one ampoule - 1000 mg per day), then immediately, without interruptions go to the reception of the drug in the form of capsules (2 capsules in the morning and one in the afternoon), which continued for six months.
Consider the dosage and duration of treatment of various chronic conditions Gliatilin capsules:

• The period of rehabilitation after a stroke - taken orally at 400 mg (1 capsule) 2 times a day, for two months.
• The early recovery period after a stroke - taken orally at 400 mg (1 capsule) 2 times a day for 2 months starting from the second week after stroke.
• The profound disturbances of movement, thought, speech and mental activity after a stroke - taken orally at 400 mg (1 capsule) 2 times a day, for six months. Start the capsules can be in the second week after suffering a stroke.
• Dementia (dementia), Alzheimer's disease and encephalopathy disease (cerebrovascular accidents) with severe motor and intellectual function - first for 5 - 14 days Gliatilin administered by injection (one ampoule 2 times a day), and then take six months inside of 400 mg (1 capsule) 2 times per day.
• Cerebrovascular accidents (encephalopathy, chronic cerebrovascular insufficiency, and others.) - Taken orally at 400 mg (1 capsule) 2 times a day for 1 - 2 months.
• Brain contusion or polytrauma (damage to various parts of the body) - within a week of the injury Gliatilin administered by injection (1 ampoule 1 time per day), then from the second week are inside of 400 mg (1 capsule) 2 times a day, within 2 months.
• Concussion - taken orally on the first day of injury 400 mg (1 capsule) 2 times a day, for a month.
• Traumatic brain injury in children - within a week of the injury Gliatilin administered by injection (1 ampoule 1 time per day), then from the second week are inside of 400 mg (1 capsule) 2 times a day for 2 months.

If the intake of capsules in humans gliatilin nausea, it is necessary to reduce the dosage of the drug and continue treatment.
These patterns of Gliatilin use are standard, but you can increase or decrease the duration of treatment, if necessary. Also, if necessary, can be carried out repeated courses of the capsules gliatilin, maintaining between intervals of at least 4 - 6 months. Remember, the longer course of therapy was - the longer should be adjourned until the next.
Injections gliatilin

The solution can be administered intravenously or intramuscularly. Gliatilin administered intravenously as an infusion ( "emitter"), the contents of the ampoule pre-diluted (4 ml) in 50 ml of saline. The finished infusion solution is introduced at a rate of 60 - 80 drops per minute.
To perform an intramuscular injection solution from the ampoule gliatilin drawn into a sterile syringe the required volume. For example, to enter the 1000 mg formulation, the syringe takes 4 - 5 ml, to select all of the solution from the vial. If it is necessary to enter only 500 mg of the drug, it takes a 2 ml syringe, ampoule to choose from only 2 ml of a solution which contained 500 mg and gliatilin.

Intramuscular injection is recommended to do in the anterior-lateral surface of the thigh, the upper outer part of the shoulder and lean people in the front abdominal wall. Not recommended intramuscular injection in the buttocks, as in this area of the body muscles lie very deep and there is a risk to introduce the solution into the subcutaneous fat layer, where the medicine will not suck the blood at a sufficient rate.
Before performing the injections necessary to process the injection site with a cotton swab dipped in antiseptic (alcohol Belasepte, chlorhexidine, etc.). Thereafter, the needle is introduced deeply into the tissue, keeping perpendicular to the skin surface. When the needle hub from the skin to remain 2 - 4 mm, needle insertion into tissue stop and start to press the plunger slowly releasing medication into the muscle. After entering all the solution into the tissue, the needle is removed, and the injection site again wiped with a cotton swab moistened with disinfectant.

The vial with the solution gliatilin should be opened immediately before use. Do not store the solution in the opened container. That is, if the ampoule has been opened, it is necessary to use either a solution or discarded. If not all of the ampoule is used for injection, the syringe gaining desired amount of solution and the remainder discarded.
Gliatilin dosage for intravenous or intramuscular injection in various diseases and the same is 1000 mg (one full ampule solution - 4 ml) at a time. Intramuscular injections were with a maximum of once per day, and intravenous - 1 - 3 times. The duration of intravenous or intramuscular injection in various diseases and also the same is 7 - 10 days. After completion of the injection rate can gliatilin immediately without interruption some other drug, move to the drug in capsules of 400 mg (1 capsule) 2 times a day for 1 - 6 months, to achieve a lasting therapeutic effect.

Injections of Gliatilin to produce better in the first half of the day, preferably before meals. The method of drug administration is determined by a physician and depends on the patient's condition. If a man is in critical condition, unconscious or unable to walk independently, it Gliatilin administered intravenously. If a person is able to walk and to adequately respond to the surrounding reality, the Gliatilin can be administered intramuscularly. However, if it is possible, it is best to apply the intravenous infusion of the drug, since this method of injection less traumatic compared with intramuscular injections.

Consider the dosage and duration of injection gliatilin a variety of conditions and diseases:

• Acute ischemic stroke - administered intravenously or intramuscularly to 1,000 mg (1 ampoule) 2 times a day for 3 - 5 days. From the second week after a stroke can start taking the capsules of 400 mg (1 capsule) 2 times a day, for a month.
• Acute period of hemorrhagic stroke - administered intravenously or intramuscularly to 1000 mg (1 ampoule) 2 times a day, for 5 - 14 days. From the second week after a stroke can start taking the capsules of 400 mg (1 capsule) 2 times a day, for a month.
• Stroke with disorder of consciousness, requiring the maintenance of vital functions - administered intravenously at 1000 mg (1 ampoule) 4 times a day at regular intervals lasting 6 hours, within 5 - 7 days.
• Dementia (dementia), Alzheimer's disease and encephalopathy (cerebrovascular accidents) with severe motor and intellectual function - within 5 - 14 days Gliatilin administered intravenously or intramuscularly in one ampoule (1,000 mg) 2 times a day, and then six months ingest 400 mg (1 capsule) 2 times per day.
• Bruising of the brain with the disorder of consciousness, requiring the maintenance of vital functions - administered intravenously at 1000 mg (1 ampoule) 4 times a day at regular intervals lasting 6 hours, within 5 - 7 days.
• Brain contusion moderate or mild, or polytrauma (trauma of several parts of the body) - administered intravenously or intramuscularly to 1,000 mg (1 ampoule) once a day for 7 days, starting from the first day of injury. Starting from the second week after the treatment of injury to continue receiving capsule 400 mg (1 capsule) 2 times a day for two months.
• Traumatic brain injury in children - be administered intravenously or intramuscularly to 1,000 mg (1 ampoule) once a day for 7 days, starting from the first day of injury. Starting from the second week after the treatment of injury to continue receiving capsule 400 mg (1 capsule) 2 times a day for two months.
• Heart disease or surgery, which can be complicated by the development of ischemic brain damage - administered intravenously or intramuscularly to 1,000 mg (1 ampoule) once a day for 3 - 7 days. The signal for introducing gliatilin in such cases is the development of the phenomenon of cardiac embolism or systemic hypotension. You can enter Gliatilin in the early postoperative period or prior to surgery to prevent complications in the form of ischemic brain damage (if there is a risk of developing such complications).

After completion of the course gliatilin injection for more persistent or significant therapeutic effect is always possible to continue treatment with taking the capsules. Capsules for various conditions and diseases to take the same dose - 400 mg (1 capsule) by two times a day for 1 - 6 months. If the condition is severe, it is permissible to take 800 mg (2 capsules) in the morning and 400 mg (1 capsule) during the day, for a month. If necessary, continue treatment after a month gliatilin receiving a daily dosage of 1200 mg (2 capsules in the morning and one in the afternoon), and the dose should be reduced by taking 400 mg (1 capsule) by two times a day for an additional 1 - 5 months. If the background of the person injecting gliatilin nausea, it is necessary to reduce the dosage of the drug and continue therapy.

Gliatilin during Pregnancy and breastfeeding
The Gliatilin drug is contraindicated during pregnancy and breastfeeding. However, if the woman is not aware of the occurrence of pregnancy, drug taking, it is not necessary to have an abortion, because animal experiments have gliatilin showed no adverse effects on the fetus. In this case, you just need to stop taking the drug immediately after it became aware of the pregnancy, and carefully do screening tests (ultrasound at 12 and 20 weeks, the concentration of the AFP test, etc.) to detect abnormalities in the developing fetus.
If a woman breast-feeding, you should take Gliatilin, the child should be converted to artificial milk formula and abandon breastfeeding.

Effects on ability to drive mechanisms
Gliatilin does not reduce the ability to control mechanisms, so the background of the drug can be engaged in any activities that require high-speed reaction and concentration.

Overdose of Gliatilin
Overdosing is possible and is shown gliatilin development of nausea, vomiting, and dyspepsia symptoms (bloating, flatulence, sensation of heaviness in the stomach, belching, diarrhea or constipation, etc.). In case of overdose it is recommended to wash out the stomach and then take a sorbent (eg activated carbon, Polisorb, Polyphepan, Filtrum, Enterosgel, etc.). Upon receipt of the sorbent needed during the day to refrain from using the drug, and then you can continue receiving gliatilin standard dosage.
Interaction with other drugs
Gliatilin not significantly interact with other drugs and therefore it can be used in combination with any other drugs.

Gliatilin for ChildrenGeneral information
Gliatilin, like other nootropics, often prescribed to young children to eliminate delays of motor, mental and speech development, and to eliminate the effects of birth trauma and perinatal encephalopathy. In more rare cases, the drug is used for the treatment of traumatic brain injury, concussion or brain injury. Children under the age of 7 years Gliatilin usually administered by injection as a solution using a necessary measure can be smaller than the dosage for adults. When using capsules a child of any age will have to give a full adult dose, because its contents are divided into several doses possible.

Gliatilin - instructions on the use of children
In various embodiments, the delays of motor, mental and speech development, perinatal encephalopathy, or the consequences of birth trauma in children of any age Gliatilin better to use in the form of intramuscular injections for several reasons. Firstly, when using a solution may be required to measure the child dosage. Second, the course of therapy injections gliatilin much shorter than when the reception tablets (so doing injections for 5 - 14 days, and drink capsules 1 - 3 months). Finally, thirdly, gliatilin injections are often much more effective than taking the capsules.
At a delay of development, the consequences of a birth trauma or perinatal encephalopathy children first year of life is administered by intramuscular injection of 1 - 2 ml solution (250 - 500 mg) gliatilin once a day for 10 - 12 days. Children aged 1 - 3 years solution was added 2 - 3 ml once a day for 10 - 12 days. A children above 3 years in adults Gliatilin dosages administered, ie, one full vial (4 ml) once a day for 10 - 12 days.
At a delay of development, the consequences of birth trauma and perinatal encephalopathy drug can be used for children and capsules. If the child is older than one year can easily swallow a whole capsule gliatilin, you should give him the drug of 400 mg (1 capsule) 2 times daily for 1 - 3 months. If the child is older than one year can not swallow the capsule, you should carefully pierce her skin needle and dial the contents of the syringe. Then all the liquid contents drawn from the capsule with a syringe, should pour into the child's mouth (after separating the needle from the syringe) and give it a non-carbonated water for drinking.
Under the same conditions of children under a year it is highly recommended to use gliatilin injection rather than capsules. However, if for any reason you have to give up the child, the preparation in the form of capsules, it is recommended to do as follows. First, the puncture needle impaled on the syringe to pull the capsule and its contents. Then, by removing the needle, gently pull the lower lip of the child and in the space between the lip and gums to drip from the syringe 4 - 6 drops of the solution, the drawn out of the capsule. Then you need to give the baby to drink. Thus the child is given preparation of 4 - 6 drops to 2 times a day for 1 - 3 months.
With traumatic brain injury, concussion or brain injury is recommended to be administered intravenously or intramuscularly Gliatilin 1000 mg (1 ampoule) once a day for 7 days, starting from the first day of injury. Starting from the second week after the injury can continue treatment taking capsules of 400 mg (1 capsule) 2 times a day, for two months.

Side effects of Gliatilin
Gliatilin usually well tolerated, and only rarely provokes the following side effects: Nausea; Allergic reactions.
When the nausea should reduce the dose gliatilin and continue taking until the end of therapy. With the development of allergic reactions need to stop taking the drug and consult a doctor.

Analogs of Gliatilin
There are analogues, which are divided into two species on the pharmaceutical market of almost every drug - synonyms and, in fact, analogs. Synonyms are drugs that, like Gliatilin, as the active substance contains choline alfoscerate. Analogues are drugs that contain other active ingredients, but they have a similar maximum gliatilin spectrum of therapeutic action.

So synonymous of Gliatilin are the following drugs: Gleatser injection; Deletions capsules, Oral solution, and the solution for injection; Nooholin Rompharm injection; Choline alfoscerate injection; Holitilin capsules and injection; Cerepro capsules and injection; Cereton capsule and injection.

Analogues gliatilin are other drugs of nootropics groups such as: Amilonosar tablets and solution for injection; Lucidril tablets; Bravinton concentrate for solution for infusion; Vinpotropil capsules, tablets and concentrate for solution for infusion; Vinpocetine tablets and concentrate for solution for infusion; Vinpocetine Forte tablets; Vintsetin tablets; Ginkgo biloba tablets and capsules; Ginkoum capsule; Glycine tablets for sublingual and buccal; Gopantam tablets; Demanol oral solution; Idebenone capsules and tablets; Cavintonum tablets and concentrate for solution for infusion; Cavintonum Forte and Cavintonum Comfort, tablets; Gopantenat Calcium tablets; Karnitex capsule; Karnicetin capsule; Cogitum oral solution; Combitropil capsule; Corsavin and Corsavin Forte tablets; Cortexin lyophilisates for solution for injection; Lucet tablets and injection; Memotropil tablets; Minis nasal drops; Neypilept injection; Neyromet capsule; Noben capsule; Hook the capsule; Nooklerin oral solution; Noopept tablets; Nootropil capsules, tablets and injectable solution; Omaron tablets; Pantogam syrup and tablets; Pantogam capsule asset; Pantokalcin tablets; Picamilon tablets and injection; Pikanoil tablets; Picogam tablets; Pineamin lyophilisates for solution for injection; Piracezin capsule; Piracetam capsules, tablets, granules for syrup for children, and the solution for injection; Piriditol tablets; Semax nasal drops; Telektol tablets; Tiocetam tablets and injection; Phezam capsule; Fenotropil tablets; Celestab capsule; Cellex solution for subcutaneous injection; Ceraxon oral solution for injection; Cerebrolisat injection; Cerebrolysin injection; Encephabol tablets and oral suspension; Epithalamin powder for solution for injection; Eskotropil solution for infusion.

Cheap analogues gliatilin cheaper drugs-synonyms gliatilin are: Gleatser injection; Nooholin Rompharm injection; Cerepro capsules and injection; Cereton capsule and injection.

Cheaper drugs, analogs gliatilin are: Vinpotropil capsules, tablets and concentrate for solution for infusion; Vinpocetine tablets and concentrate for solution for infusion; Ginkgo biloba tablets and capsules; Glycine tablets for sublingual and buccal; Gopantam tablets; Cavintonum tablets and concentrate for solution for infusion; Gopantenat Calcium tablets; Corsavin and Corsavin Forte tablets; Lutset tablets and injection; Memotropil tablets; Noben capsule; Nooklerin oral solution; Noopept tablets; Nootropil capsules, tablets and injectable solution; Omaron tablets; Pikamilon tablets and injection; Pikogam tablets; Piracetam capsules, tablets, granules for syrup for children, and the solution for injection; Telektol tablets; Tiocetam tablets and injection; Phezam capsule.

Better than gliatilin
In medical practice, there is no concept of the "best" or "better" in relation to drugs. Instead, doctors use the term "optimal". Under optimal drug understand that the person best suited and gives the most pronounced therapeutic effects in real time. This means that one person will be optimal Gliatilin, for another - Pantokalcin, and for the third - Encephabol etc. Moreover, for the same person at different times may have different optimum preparations, for example, two years ago it was Gliatilin, and now - Pantokalcin. But it is the best drug is best for a person. Given the very wide variability in optimal drugs as defined by the individual characteristics of the organism, to determine a drug that is better for all people gliatilin not possible.

Gliatilin Reviews

Reviews gliatilin in most cases are positive, as the drug provides a pronounced therapeutic effect. For example, in a review of people who took the drug for improvement of cognitive abilities on the background of a busy schedule, it is noted that Gliatilin normalize state regained vigor and high performance, improved memory, attention and productivity of thought, so that even the hard and long work is not exhausting, and the head end of the day remained bright and "good to think."

People who took the drug to eliminate the consequences of stroke or traumatic brain injury, as well as for improving cognitive abilities (memory, attention and thinking), regressed against various diseases (eg, senile degenerative changes in the brain tissue, cerebral circulatory insufficiency, etc. .), point out that Gliatilin improved their condition and state of health.
So, the increased stroke volume movements on the side of paralysis, improve memory and attention, thinking becomes more even, not torn, etc. People who have had a head injury, the drug to normalize consciousness, managed to remove the headaches and dizziness. But in people suffering from various diseases, provoking deterioration of cognitive abilities, Gliatilin significantly improves concentration, long-term and short-term memory, thinking and doing more productive and not torn.
Negative reviews about gliatilin bit, and in most cases they are due to the development of allergic reactions or severe tolerability of the drug. Furthermore, many people in the review indicate that injections given apparent therapeutic effect after administration of capsules and does not feel any positive changes. In this regard, the review often concluded that better use gliatilin injection and capsule to take it is not necessary due to the lack of therapeutic effect.

Gliatilin - reviews for children
More than 2/3 (70 - 78%) reviews the application gliatilin children are positive, due to the good therapeutic effect of the drug in the treatment of developmental delay. For example, in a review indicates that after a course of application gliatilin children started to speak better, increased vocabulary, improved pronunciation of words appear longer and lucid phrases or sentences in the speech, etc. As other reviews stated that Gliatilin literally gave impetus to the development of the baby, who, after a course of therapy began to sit up, roll over, crawl, stand up on its feet, walking, etc. Since Gliatilin most commonly used to treat delayed child development, and reviews of preparation relate almost exclusively of this aspect. Reviews on the application gliatilin in children for the treatment of traumatic brain injury, brain injury, etc. -. No.
Negative reviews about gliatilin for children due to a number of factors. First, the negative reviews left by parents whose children are poorly tolerated drug, grew during the reception restless, constantly crying, complaining of a headache, etc. Second, the negative reviews are left by parents who have not received from gliatilin the expected therapeutic effect.
In addition, there are negative reviews about it gliatilin capsules. In such a review, parents indicate that injections course provides significant and visible effect, and after receiving the capsule did not have any noticeable changes.

Cogitum - instructions for use (adults and children), analogs, reviews

The drug Cogitum

Cogitum refers to the adaptogenic and tonic funds, reducing the central nervous system. The active ingredient of this drug is potassium-amino-acetyl succinate, which is able to drive acetyl-amino-succinic acid contained in the CNS tissues and is responsible for the normal transmission of nerve impulses. Such effects on the human organism leads to the normalization of all stimulation and regulation of nervous processes.

Cogitum also can participate in the synthesis of RNA and DNA, to improve physical endurance and stimulate the immune system, speeding up the processes of formation of antibodies and immunoglobulins.
Revealed and such properties of this drug, which point to its ability to provide a hepatoprotective effect, accelerate the excretion of ammonia (in case of poisoning them) and reduce the negative impact of radiation on tissue.
Manufacturers Cogitum preparation are the three French companies: Patheon France, Hoechst Marion Roussel / Marion Merrell and Sanofi-Aventis.

Cogitum Release Form

Cogitum is produced in the form of a clear solution of light yellow color for ingestion. The solution has a pleasant banana flavor and is packaged in vials of dark glass with pointed ends.
Cogitum ampoule 250 mg / 10 ml (25 potassium-amino-acetyl succinate1 mL), placed in plastic packaging cells - 30 ampoules per carton.

Instructions for use Cogitum
Indications

• Functional asthenic conditions;
• Depression and nervous disorders in mild;
• Antidepressants;
• Fatigue.

In most cases, Cogitum is used in the complex therapy. In pediatric practice reading list of more extensive.

Contraindications for Cogitum: Hypersensitivity to one of the components of the drug; children up to 7 years.

Side effects of Cogitum: Allergic reactions such as rash or itchy skin. In most cases, the drug was well tolerated, and allergic reactions are extremely rare.

Cogitum Treatment
How to take Cogitum?

The drug is intended for oral administration (internal) use. Most preferably carried out its welcome in the morning. Cogitum has a pleasant taste and can be used without dilution with water (at a dilution in water the taste almost completely lost). Breeding of drinking water preparation, with the convenience of its acceptance as such, are not prohibited.
Before taking Cogitum necessary to open the ampoule at one end, placing it on a glass or cup, and break off the lower end of the ampoule. The solution seamlessly result in cooked dishes.
Omitting one or more methods of drug treatment Cogitum can continue in the same doses that were prescribed by a doctor (no need to accept the missed dose).
The drug can stop suddenly, this will not cause any serious or unpleasant symptoms.
Dosage of Cogitum
Dosage and duration of treatment in most cases the individual is assigned.
The average adult dose is 3 capsules in the knocks. In this take 2 capsules in the morning and 1 vial - before going to bed.
The average duration of treatment Cogitum is 3 weeks, and if necessary, your doctor may prescribe a second course of treatment after a certain period of time.

Cogitum for children
Cogitum is used in pediatric patients for the treatment of different neurological, psychiatric diseases and conditions in children older than 7 years. Clinical data on the admission of the drug in children under 7 years not.
Indications for admission Cogitum in pediatrics quite extensive:

• delay stages of physical development;
• delay emotional, psychomotor,
• pre-speech and speech development;
•  mental retardation; syndrome, perinatal lesions of the nervous system;
• neurotic disorders;
• short-term depression;
• adjustment disorder;
• syndrome of fatigue after a viral disease; consequences of traumatic brain injury or neuroinfections;
• mental development disorders; periods of high emotional, physical or mental exertion.

Dosing of Cogitum, the definition of the duration of his admission and the need for repeated courses of receiving the appointment of children in most cases is determined individually and depends on the age and the child's diagnosis.
Average dose of Cogitum: for children 7-10 years - 1 ampoule in the morning; Children 10-18 years - 2 capsules in the morning.
The average duration of treatment Cogitum in children from 2 weeks to a month.

Cogitum during pregnancy and lactation
Cogitum can be administered during pregnancy and lactation only on doctor's advice, although studies have not revealed teratogenic, mutagenic or embryotoxic effects of the drug. In appointing Cogitum nursing mothers may need to cancel breastfeeding.

Drug Cogitum Interactions
In clinical trials there was no evidence Cogitum ability to interact with other drugs.

Analogs of Cogitum
Cogitum analogs that are completely identical in composition exists. If necessary, your doctor may prescribe this drug instead of other drugs with similar indications for use.

Reviews about Cogitum
Reviews for admission Cogitum different - from positive with excellent results up sharply negative. On some forums there are information that consumers are often faced with the fakes of this drug, and it could only buy with a doctor in a hospital or private individuals.
Reviews of the treatment of adult Cogitum (if all the doctor's instructions) is mainly positive. They note: the drug's effectiveness in eliminating signs of fatigue, nervousness and depression, ease of reception and a pleasant taste. Reviews of adverse allergic reactions are extremely rare.
Rare negative reviews about this preparation contain information about the absence of the desired effect and may be due to incorrect assignment of the drug or breach the basic scheme of complex treatment.
Reviews Cogitum treatment of children with delayed speech development in the most positive. Many parents of young patients note: the rapid expansion of the vocabulary of the child, the emergence of the ability to construct sentences and more productive perception and assimilation of new information.

If you are using this medication to correct problems with the pronunciation, in the opinion of parents, positive results were observed rarely, t. To. This pathology is increasingly in need of speech therapy remedial work on the speech of the child.
In appointing Cogitum children to eliminate nervousness, fatigue, emotional, mental or physical stress by the majority of parents were positive results. The good effect is observed and when taking this drug to restore the overall health of children after craniocerebral trauma, viral diseases and neuroinfections. Reviews of the occurrence of an allergic reaction to Cogitum in children are extremely rare.

Some parents have noted that taking Cogituma can cause symptoms of hyperactivity in children, moodiness, sleep disturbances, nervousness (even tantrums and aggression). Described isolated cases and the appearance of seizures in children with a history of epileptic seizures. Smooth data negative manifestations, according to many moms, helps the following activities: a parallel reception of this preparation as Magne B6, gradual increase of dosage Cogitum and its phasing out, the reception of the solution only in the morning or no later than 3 pm.
Reviews parents of children who are appointed Cogitum, point to the fact that this drug, despite the presence of contraindications in the instructions intended for children up to 7 years, in practice, is used to treat and at an earlier age (3-4 years old, and even isolated cases of appointment children up to a year). In such cases, the appointment of Cogitum can be carried out only with the written consent of the parents.
Most Cogitum patients assessed as "an expensive drug."

Bromdihydrochlorphenylbenzodiazepine - Active Substances. Instruction and Application, Dosage

Name: Bromdihydrochlorphenylbenzodiazepine

The Latin name of the substance Bromdihydrochlorphenylbenzodiazepine

Bromdihydrochlorphenylbenzodiazepinum (genus Bromdihydrochlorphenylbenzodiazepini)

Chemical name: 7-Bromo-5- (2-chlorophenyl) -1,3-dihydro-2H-1,4-benzodiazepin-2-one

Formula - C15H10BrClN2O

Therapeutic substances Bromdihydrochlorphenylbenzodiazepine- anxiolytics

The nosological classification (ICD-10)

F00 Dementia in Alzheimer's disease (G30 +)
F03 Unspecified Dementia
F05 Delirium, not induced by alcohol or other psychoactive substances
F07.2 Post-contusion syndrome
F10.3 abstinence
F11 Mental and behavioral disorders due to use of opioids
F20 Schizophrenia
F23 Acute and transient psychotic disorders
F25 Schizoaffective disorders
F30 Manic episode
F32 Depressive episode
F40.0 Agoraphobia
F40.8 Other phobic anxiety disorders
F41.0 Panic disorder [episodic paroxysmal anxiety]
F41.1 Generalized anxiety disorder
F42 Obsessive-compulsive disorder
F43.0 Acute stress reaction
F43.1 Post-traumatic stress disorder
F43.2 Disorder adaptive reactions
F44 Dissociative [conversion] disorders
F45 Somatoform disorders
F45.2 Hypochondriacal disorder
F48 Other neurotic disorders
F51.0 Insomnia inorganic etiology
F60 Specific personality disorders
F60.2 antisocial personality disorder
F60.3 Emotionally unstable personality disorder
F63 Disorders of habit and impulse
F79 Mental retardation, unspecified
F95 Teaks
G40 Epilepsy
G41 Status epilepticus
G47.0 Disorders of falling asleep and maintaining sleep [insomnia]
R25.2 Cramp and spasm
R45.0 Nervousness
R45.4 Irritability and anger
Z100 * CLASS XXII Surgical practice

CAS code - 1753-57-2

Characteristics substance Bromdihydrochlorphenylbenzodiazepine
Anxiolytic.
White or light white crystalline powder. Practically insoluble in water and ether, slightly soluble in ethanol, it is difficult in chloroform.

Pharmacology of Bromdihydrochlorphenylbenzodiazepine
Mode of action - anxiolytic, anticonvulsant, muscle relaxant, central, hypnotic, sedative.
Stimulates the benzodiazepine receptors, it increases the sensitivity of GABA receptors to mediator, increases the braking effect of GABA in the CNS. Reduces the excitability of the subcortical brain structures inhibits polysynaptic spinal reflexes. It reduces emotional stress, reduces anxiety, fear, anxiety. It suppresses the spread of excitation arising in the epileptogenic foci in the cortex, the thalamus, and limbic structures of the brain by increasing presynaptic inhibition (increased focus activity is not reduced).

Well absorbed from the gastrointestinal tract. Time to reach C max -. 1-2 hours is metabolized in the liver. T1 / 2 -. 6-10 hours excreted by the kidneys. Reduced liver and kidney function slows down the clearance and leads to accumulation.

Application of the Bromdihydrochlorphenylbenzodiazepine substance

Neurotic, neurosis, psychopathic and psychopathic state, accompanied by anxiety, fear, increased irritability, tension, and emotional lability; sleep disorders, obsessive-compulsive disorder, panic disorder, phobias, reactive psychosis; vegetative lability, hypochondriacally-senestopatic syndrome; seizures of various etiologies, temporal and myoclonic epilepsy, status epilepticus, muscle rigidity, teak, athetosis, hyperkinesis; premedication (as a component of induction of anesthesia); in the complex therapy of opioid and for abuse syndrome, schizophrenia (febrile form, increased sensitivity to antipsychotics); prophylaxis of conditions of fear and emotional stress.

Contraindications of Bromdihydrochlorphenylbenzodiazepine
Severe myasthenia gravis, severe liver damage (cirrhosis, infectious disease) and kidneys; poisoning other tranquilizers, antipsychotics, hypnotics, narcotics, alcohol.; pregnancy, breast-feeding.

Pregnancy and breast-feeding
Contraindicated during pregnancy. At the time of treatment should stop breastfeeding.

Side effects of Bromdihydrochlorphenylbenzodiazepine substance
From the nervous system and sensory organs: dizziness, headache, drowsiness, muscle weakness, impaired memory, concentration, coordination, paradoxical excitement, ataxia, mydriasis.
From the digestive tract: dry mouth, nausea, diarrhea.

Allergic reactions: skin rash, pruritus.

Other: dysuria, dysmenorrhea, loss of libido, addiction, drug dependency.

Interaction of Bromdihydrochlorphenylbenzodiazepine

(Mutually) effect of neuroleptics, tranquilizers, sleeping pills, narcotic, analgesic, anticonvulsant drugs, and alcohol.

Overdose of Bromdihydrochlorphenylbenzodiazepine

Symptoms: marked depression of consciousness, cardiac and respiratory activity.

Treatment: control of vital functions, maintaining respiratory and cardiovascular activity, symptomatic therapy. Specific antagonist flumazenil (w / 0.2 mg - optionally up to 1 mg - 5% glucose solution or 0.9% sodium chloride solution).

Dosing and Administration of Bromdihydrochlorphenylbenzodiazepine
Inside, in / m or / in (bolus or infusion). The mode set is strictly individual, depending on the indications of the disease, tolerance and others.

For quick relief of fear, anxiety, psychomotor agitation, as well as autonomic epileptic and psychotic states: in / m or / in, the initial dose for adults - 0.5-1 mg (0.5-1 ml of 0.1% solution ), the average daily - 3-5 mg, in severe cases, up to 7-9 mg. Premedication: / slow 4.3 mg (3.4 ml of a 0.1% solution).

When administered a single dose for adults is usually 0.5-1 mg (with sleep disorders - 0.25-0.5 mg), the average daily - 1.5-5 mg 2-3 hours (typically 0.5 -1 mg in the morning and during the day and 2.5 mg at night), the maximum daily - 10 mg.

Neurotic, neurosis, psychopathic and psychopathic states: Inside, the initial dose of 0.5-1 mg 2-3 times a day, 2-3 days (if necessary) - up to 4-6 mg / day; in severe agitation initial dose - 3 mg / day, then rapidly increasing the dose until a therapeutic effect.

Neurological Practice (disease with increased muscle tone), inside of 2-3 mg 1-2 times a day or in / m, 0.5 mg 1-2 times a day.

Status epilepticus, serial seizures: in / m or / in, starting with a dose of 0.5 mg. In the treatment of epilepsy - 2.10 mg / day.

Alcohol withdrawal: inside, 2.5-5 mg / day.

The course of treatment with oral - 2 weeks (if necessary - up to 2 months), at parenteral administration - up to 3-4 weeks. To use caution in the elderly and in children (a daily dose reduced by a factor of 2-3).

Precautions substance Bromdihydrochlorphenylbenzodiazepine

Note that the combination of anxiety with depression may attempt suicide.

To apply caution in conjunction with other psychotropic drugs. Should not be administered concurrently with MAO inhibitors and phenothiazines.

With prolonged use (over several months), particularly at high doses, may addiction, drug dependence. Abolition of chlordiazepoxide should be done gradually by reducing the dose to reduce the risk of withdrawal syndrome characterized by tremor, cramps, abdominal and muscle cramps, vomiting, sweating. In abrupt cancellation also possible agitation, anxiety, autonomic disorders, insomnia.

Do not take chlordiazepoxide more than 4 weeks without re-evaluation of the patient to decide whether to continue therapy.

The probability of side effects is higher in the elderly.

Prolonged use should be periodically monitored picture peripheral blood and liver function.

There are reports that in the treatment of chlordiazepoxide mental patients and children with the aggressive behavior traits observed paradoxical reactions (psychomotor agitation, rage, etc.).. In the case of paradoxical reactions, treatment should be discontinued immediately.

It should be borne in mind that chlordiazepoxide can reduce mental alertness in children.

It must be borne in mind that there are reports of effects on blood coagulation in patients taking oral anticoagulants simultaneously and chlordiazepoxide (in a clinical study of the causes and consequences of this interaction has not been established). There are some reports of exacerbation of porphyria under the action of chlordiazepoxide. Hypoproteinemia may predispose to increase the frequency of sedative side effects.

During treatment and for 3 days after its cancellation should be deleted reception alcohol; drivers of vehicles and people whose work requires quick mental and physical reactions, and is also associated with high concentration of attention, should not engage in professional activities during this period.

Special instructions for Bromdihydrochlorphenylbenzodiazepine
As an equalizer avoids or reduces some of the side effects that can be applied mesocarb. Be wary of the organic cerebral insufficiency. The lifting should be done gradually by reducing the dose to reduce the risk of withdrawal symptoms.

Should not be used during the drivers of vehicles and people skills relate to the high concentration of attention. At the time of treatment should abandon admission alcohol.

Trading names of drugs with Bromdihydrochlorphenylbenzodiazepine working substance

Trade Name Index 

Bromdihydrochlorphenylbenzodiazepine,Trankvezipam, Phezanef, Phezipam, Phenazepam tablets, phenazepam, Phenzitat, Phenorelaxan, Elzepam

Hydroxyzine - Active Substances. Instruction and Application, Dosage

Name: Hydroxyzine

The Latin name of the substance Hydroxyzine

Hydroxyzinum (genus Hydroxyzini)

Chemical name: 2- [2- [4 - [(4-chlorophenyl) phenylmethyl] -1-piperazinyl] ethoxy] ethanol (as the dihydrochloride or embonate)

Formula - C21H27ClN2O2

Therapeutic substances Hydroxyzine - anxiolytics

The nosological classification (ICD-10)

F10.2 alcohol dependence syndrome
F10.3 abstinence
F11 Mental and behavioral disorders due to use of opioids
F41.1 Generalized anxiety disorder
F43.0 Acute stress reaction
L29 Itching
R45.1 Restlessness and agitation
R45.4 Irritability and anger
R45.7 State of emotional shock and stress, unspecified
Z100 * CLASS XXII Surgical practice

CAS code - 68-88-2

Characteristics substance Hydroxyzine
Diphenylmethane derivative. Hydroxyzine hydrochloride - white powder, odorless, very soluble in water, the molecular weight of 447.83.

PharmacologyMode of action - a sedative, anxiolytic.

It inhibits the activity of certain subcortical structures of the central nervous system, blocking the central m-choline and of H1-histamine receptors.

Characterized by pronounced sedative effects and moderate anxiolytic activity. It has a positive influence on cognitive abilities, improves memory and attention. It does not cause mental dependence and addiction, chronic administration were observed withdrawal. It has also an anticholinergic, antispasmodic, anti-histamine effect. It relaxes smooth muscles, has a bronchodilator and analgesic effect, has antiemetic, and muscle relaxant action and a moderate inhibitory effect on gastric secretion. Reduces itching hives, eczema, dermatitis and others.

Sedation is usually observed after 10-45 min after oral administration (depending on formulation), antihistamine - 1 hour after ingestion. Patients with liver disease anti-histamine effect can last up to 96 hours.

Mutagenic and carcinogenic effects have been identified.

Introduction hydroxyzine pregnant female rodents (mice, rats, rabbits) at doses much higher than the therapeutic dose for humans, led to the emergence of fetal malformations in the fetus.

If ingestion is rapidly absorbed from the gastrointestinal tract, the Cmax is achieved in 2 hours. Passes through GEB and placenta (in fetal tissues is concentrated to a greater extent than the parent). It is metabolized in the liver, the major metabolite - cetirizine. T1 / 2 depends on the age of the patient and is 7 hours (in children 2-10 years), 20 hours (adults), 29 hours (in the elderly and elderly); in patients with liver disease increased to 37 h. Write mainly kidneys (0.8% unchanged).

Application of the substance Hydroxyzine

Relief of anxiety, agitation, inner tension, irritability, neurological, mental (generalized anxiety and adjustment disorders) and somatic diseases; alcohol withdrawal syndrome; premedication and postoperative period (in combination therapy); itching (symptomatic therapy).

Contraindications

Hypersensitivity, including to cetirizine, aminophylline or ethylenediamine; porphyria, pregnancy, labor and delivery, breast-feeding.

Restrictions of application of Hydroxyzine

Glaucoma, prostatic hypertrophy with clinical symptoms (including difficulty urinating, constipation), myasthenia gravis, dementia, susceptibility to seizures, kidney and / or liver failure.

Pregnancy and breast-feeding
Contraindicated during pregnancy.

Category effects on the fetus by FDA - is not defined.

At the time of treatment should stop breastfeeding (unknown if excreted into breast milk).

Side effects of Hydroxyzine substance 

From the nervous system and sensory organs: drowsiness, weakness (in the early days of admission), headache, dizziness.

Other: increased sweating, tachycardia, nausea, allergic reactions, dry mouth, urinary retention, constipation, eye accommodation.

Interaction

It is dampening effect on the central nervous system narcotic analgesics, barbiturates, tranquilizers, hypnotics (individual selection of doses required), alcohol. Prevents the development of the pressor effect of epinephrine, anticonvulsant activity of phenytoin, the action of betahistine and cholinesterase blockers. Reduces side effects (from the stomach), theophylline and beta2-agonists.

Interactions with drugs that cause changes in the ECG
Hydroxyzine in high doses may cause disturbances ECG, including lengthening the interval QT, so concomitant use with other drugs capable of causing cardiac abnormalities may increase the likelihood of arrhythmias and sudden death.

Clinical evidence, mechanism, importance and caution
In 25 elderly patients with psychosis treated with hydroxyzine 300 mg, ECG changes after 9 weeks were moderate, with the exception of T-wave changes (detected in 9 people and is usually observed in the position 1,2 AVL and V1-6). In each case, T wave height was reduced, expanded, flattened; QT interval is usually extended. At repeated research in a few patients, one of whom received 400 mg of hydroxyzine, similar results were obtained, with more pronounced changes, which consisted of a marked weakening of the myocardial repolarization. Please pay attention to Noopept.

On the basis of these observations, it is assumed that other drugs that cause changes in the ECG (antiparkinsonian drugs, atropine, lithium carbonate, phenothiazines, quinidine, procainamide, thioridazine, tricyclic antidepressants) may intensify and exacerbate the changes caused by Hydroxyzine, and increase the risk of sudden death. Further study is needed to evaluate the practical significance of these possible interactions. However, you should avoid joint use of two or more drugs prolonging the QT interval, due to the risk of additive effects, which may lead to severe and potentially life-threatening cardiac arrhythmias, such as a pirouette.

Overdose of Hydroxyzine

Symptoms: hyper-sedation, tremor, convulsions, hallucinations, confusion, low blood pressure, nausea, vomiting.

Treatment: induction vomiting (in the absence of spontaneous), gastric lavage, general supportive measures, including monitoring of vital body functions. If hypotension - introduction of norepinephrine (but not epinephrine). There is no specific antidote. Hemodialysis is ineffective.

Dosing and Administration of Hydroxyzine

Inside, in / m. Adults: in general practice - 25-100 mg / day in divided doses, in psychiatry - up to 300 mg / day. The usual duration of the course of treatment - 4 weeks. In anesthesiology: / m, adults - 100-200 mg / day, for sedation - 50-200 mg.

Children appoint depending on the age and body weight.

In simultaneous treatment means, oppressive central nervous system, or holinoblokatorami, need a dose adjustment. The dose should be reduced in elderly patients (treatment start with half the therapeutic dose), renal and liver failure.

Precautions substance Hydroxyzine
If side effects such as sleepiness and weakness do not disappear after a few days of treatment, the dose should be reduced. Avoid joint appointment with MAO inhibitors. To use caution in patients prone to arrhythmia or receiving antiarrhythmic drugs, and in patients prone to convulsive reactions.

During treatment should avoid drinking alcohol. When the need for allergy tests receiving hydroxyzine should be discontinued 5 days prior to the study. Be wary of during the drivers of vehicles and people skills relate to the high concentration of attention.

Special instructions for Hydroxyzine
Injectable forms of hydroxyzine are only for i / m injection and should not be administered in / in / and or s / c. When i / m administration should make sure that the needle does not hit in any vessel. When administered to the skin the drug may cause tissue damage.

Trading names of drugs with Hydroxyzine working substance

Trade Name Index 

Atarax, Hydroxyzine, Hydroxyzine Canon, Hydroxyzine hydrochloride

Paracetamol + Codeine (Codelmicst)

Pharmacological group: analgesics; analgesics opioids; Non-narcotic analgesics

Pharmacological action: combined drug whose action is due to the effects of its constituent components. Paracetamol has analgesic and antipyretic activity. Codeine has a central antitussive effect (excitability by inhibiting cough center), and the analgesic effect due to the excitation of opioid receptors in various parts of the CNS and peripheral tissues, resulting in stimulation of antinociceptive system and change the emotional perception of a pain. To a lesser extent than morphine respiratory depression, less likely to cause miosis, nausea, vomiting and constipation (opioid receptor activation in the intestine causes relaxation of smooth muscle, reduction of motility and sphincter spasm). Duration of Analgesic Effect - 4 hours, antitussive - 4.6 hours.
The impact on the receptors: the opiate receptors
Legal status: available only on prescription; List III (US)
Application: oral

Codelmicst analgesic is composed of a combination of codeine phosphate and paracetamol (acetaminophen). Codelmicst tablets used to relieve mild to moderate pain, or when paracetamol NSAIDs (nonsteroidal antiinflammatory drugs) such as ibuprofen, naproxen or aspirin, do not themselves cause sufficient relief of symptoms. Codelmicst is sold under various brand names.

The compositions of Codelmicst
There are seven variants of dosing:

8 mg codeine phosphate tablet (e.g., Tylenol 1 in USA / Canada)
Codeine phosphate 10 mg per tablet
Codeine phosphate 12.8 mg per tablet
15 mg of codeine phosphate per tablet (for example, 2 brands of Tylenol in the US / Canada, Norway, Australia (several brands), Great Britain)
20 mg of codeine phosphate per tablet (Prontalgine in France, Empacod, South Africa and Zimbabwe)
30 mg codeine phosphate tablet (e.g., Tylenol 3 in USA / Canada - Emtec-30 or "Emtec" in Canada is available in capsules such as Tylex or in the form of tablets / capsules Solpadol, for example, Kapake, Panacod and Zapain).
Codeine phosphate 60 mg per tablet (e.g., Tylenol 4 in USA / Canada, usually contain from 300 to 1000 mg (1 g) [[paracetamol | paracetamol]] per tablet. You can also like Ladasten.

In the United Kingdom a prescription dispensed tablets 15/500 and 30/500, but without the prescription form available at 8/500 and 12.8 / 500. In Australia, only prescription tablets dispensed 30/500 and 10/500. Tablets 15/500 included in List 3 (that is, these drugs for pharmacists only). The instructions from the manufacturer recommended not to exceed the recommended doses - two tablets every four hours and a maximum of eight tablets (8h500 mg) in a 24-hour period and no more than two (2x500 mg) for one time. Unless otherwise prescribed by your doctor or pharmacist to avoid other drugs containing acetaminophen. Excessive amounts of acetaminophen can cause serious liver damage. Kodelmikst sold in Canada and the United States are also under the title «Atasol Codeine». In the UK, it is marketed under the brand name «Solpadeine Plus» and «Solpadeine Max», and «Solpadol». In Australia - as the «Panadeine», «Panadeine Extra» and «Panadeine Forte». Kodelmikst sold under the trademarks «Paralgin Minor» (15/200), «Paralgin Forte» (30/400), «Paralgin Major» (60/800), «Pinex Forte» (30/500) and «Pinex Major» ( 60/1000) in Norway.

Side effects
Side effects may include constipation, skin rash, dizziness, sedation, shortness of breath, hypersensitivity reactions, syncope (fainting or presyncopal state), nausea and / or vomiting, confusion, short term memory loss, drowsiness, changes in the blood, allergic reactions, euphoria , dysphoria, abdominal pain, itching, easy bruising, bleeding gums, dry mouth, and addictive. Genetic differences between individuals lead to a different rate of metabolism of codeine to morphine. Approximately 5% of people have this metabolism may be particularly fast, which leads to higher levels of morphine transmitted through breast milk in quantities that could potentially lead to fatal respiratory oppression child through breastfeeding.

Availability:
From 1 June 2012 Russia imposed a ban on the sale of drugs codeine without a prescription. Codelmicst is a combination of paracetamol and codeine, and is released from pharmacies only by prescription.

Modafinil

Modafinil is a prescription drug for narcolepsy, increases concentration and eliminates sleepiness also increases the perception and memory abilities. Modafinil as a dietary supplement takes pride of place among nootropics. Modafinil is a drug to get rid of sleepiness during the day and for the treatment of narcolepsy. Perhaps the improvement of perception by stimulating neurotransmitters in the brain, used to improve mental abilities.

Pharmacological group: stimulants; psychostimulants; nootropics. Mode of action: the treatment of narcolepsy, sleep apnea and other sleep disorders. The impact on the receptors: α1-adrenergic receptors (agonist) is also known as: 2- (diphenylmethyl) sulfinyl acetamide, Provigil, Modalert, Modapro, Alertex.

Not to be confused with Adrafinil!

In the US and Canada, modafinil is issued strictly on the recipe and get it not so easy, its distribution is strictly controlled in the United States.
• Belongs to nootropics

Modafinil: instructions for use
The standard dose is 100-200mg, or 4 mg per kilogram of body weight, take in the event of deliberate suppression of sleep or after waking up in the morning to maintain a cheerful state and without any harm to sleep at night.

In clinical use for the treatment of excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea, the recommended dosage usually ranging from 200 to 400 mg per day. The dose may be taken once in the morning or in two divided doses (morning and noon). When used to enhance physical performance, typical effective dosage is in the range of 100-400 mg. The drug is often taken for 2-3 hours before sporting events. Note that the side effects are dose dependent. Often advised to start using modafinil at the minimum effective dose and increase it by 50-100 mg per reception to establish optimum level. Areas of application of the drug are enormous and, in fact, include all kinds of sports, focusing on aerobic exercise or stamina. It is also great for athletes, performing exercises for strength or speed in short intervals repetitions (anaerobic load), such as the shot put, pole vault and long jump. Modafinil drug is not popular among builders, since it does not directly affect an increase in muscle or fat reduction levels in the body. Some, however, believe that the drug is effective stimulant before a workout, especially during periods of fatigue or loss of physical activity after hard work or because of other reasons.

Description pf Modafinil
Modafinil or benzhydrylsulfinylcetamid - central stimulant (psychostimulant). The substance approved by the FDA for the treatment of narcolepsy (a disease characterized by sudden and uncontrollable episodes of deep sleep, fatigue or excessive sleepiness), sleep apnea, and sleep disturbances caused by changes in the operation. quality tests were performed medication, including, as an agent for treating Alzheimer's disease, depression, and attention deficit disorder. Modafinil belongs to a group of drugs known as evgeroiki (stimulators) that promote mental alertness and attention. One of the known mechanisms of action of these drugs is agonism alpha 1-adrenoceptor, resulting in drugs have an influence on the mood, increasing the power by increasing dopamine release in the central nervous system. This also leads to changes in the levels of glutamate and GABA. In studies of modafinil were as stimulant drug shows advantages compared to amphetamine. To begin with, that the substance is supposed to have a much lower potential for abuse due to the fact that the impact does not cause the same euphoria. Moreover, the drug has minimal effect on peripheral CNS stimulation (i.e., exhibit less side effects), it has a minimal effect on the blood pressure does not cause sleep interruptions (without hangover or needs "catch" sleep), and, according to clinical trials, It has a more robust safety profile. The drug is used by the US armed forces even as an energy stimulant for pilots and soldiers required to operate for long periods of time without sleep. This is not as strange as it may seem at first glance, since the last military pilots and soldiers is widely used Dexedrine (Amphetamine) during long periods of sleep deprivation. Soldiers who use modafinil, often report that the drug helps them to maintain excellent cognitive function for up to 40 hours without sleep, and has fewer side effects than Dexedrine. Modafinil has been tested the last combat situations, such as Afghanistan and Iraq, and possibly in the future will receive official recognition as a special preparation for the military. Recently, modafinil became known among competitive athletes. They use it not only as a preparation for the "courage", and as a stimulant that increases the performance and endurance. Such use is likely to be a surprise for this drug developers, as it was reported earlier that the "soft" drug enhancing the vigilance does not have strong stimulatory effects, and can not improve athletic performance. Recent studies contradict these statements. A study in Canada found that taking modafinil can provide a pronounced sporting advantage. In a double blind study 15 male volunteers took the drug at a dose of 4 mg per kg body weight (equivalent to 200 mg for a person weighing 220 pounds) or placebo. Three hours after the meal held aerobic exercise on a cycle ergometer at 85% of maximal aerobic capacity, up to exhaustion. Taking modafinil men could exercise over a much longer periods of time (up to 30% longer), and used more oxygen intake during exercise. Also reported a decrease in the perceived intensity, whereby there is an increase in exercise performance. Please pay attention to Ladasten.

History of Modafinil
Modafinil was developed by Lafon Laboratories in France. In 1998, the drug was approved by the FDA for sale in the United States, where it is sold under the brand name Provigil. Modafinil is also found on the international market for this and certain other trade names, including Modiodal, Vigil, Alertec and Modasomil. Although the drug has a favorable safety profile in the United States for some time, he was considered a drug capable of provoking possible abuse. Currently Modafinil is included in Schedule IV controlled substance, along with Valium and Xanax. For example, its use for non-medical purposes is limited by significant legal sanctions on the import and possession of the drug. The drug has a fairly broad medical use, including sleep disturbances associated with changes in the operation. The drug is often prescribed prescription. In 2000-2004 Modafinil has become popular among competitive athletes before athletic regulatory authorities have not begun to show concern about the use of the drug. In 2004 he broke out the doping scandal involving the company VALCO, when it became known that many of the athletes who gave a positive result in the use of tetragidrogestrinona also used and Modafinil. After that, the IOC prohibits the use of modafinil, and through a series of research methodology of detection of this chemical in the urine was developed. Now that testing is part of the standard survey of athletes before the Olympic competition. Most other international sporting bodies followed the example of the IOC and the ban on testing of modafinil. Since then, the drug has lost its appeal as an "invisible" in tests, although still used by many athletes, not passing urine sample testing.

How Modafinil supplied
Modafinil often supplied as tablets of 100 mg and 200 mg each.

Structural Features
Modafinil is a central nervous system stimulant, close to adrafinilu. It has the chemical name 2 [(diphenylmethyl) sulfinyl] acetamide.

Structure and Properties of Modafinil
Origin
Modafinil is a drug for the treatment of diseases associated with sleep disorders and also improves the mental state during the long wakefulness.

Modafinil forms
The term "modafinil" refers to a racemic mixture of two isomers, R-S-modafinil and modafinil. R-isomer is referred armodafinilom. Modafinil is a racemic mixture of S-R-modafinil and modafinil, armodafinil while is represented only R-modafinil.

Pharmacology
serum
The half-life of modafinil is 13-15 hours, and serum concentration at steady state up to 2 days after the start of the reception. Half-life of S-isomer of modafinil is 4-5 hours, while the R-isomer of modafinil is longer period (15 hours) and thereby receiving substantially equivalent armodafinil receiving modafinil. These experiments showed that the concentration in the blood armodafinila 18% percent greater than in the case of modafinil (5.44 +/- 1.64mg / ml versus 4.61 +/- 0.73mg / mL) and accumulate in a shorter period of time (1.8 hours versus 2.5 hours) and the total concentration in urine armodafinila up 32-40%. Although both options modafinil (modafinil and armodafinil) have the same half-life, the effect on the body armodafinila is stronger (according to the content in the urine and blood).

Localization
According immunocytochemistry gene c-Fos (the gene responsible for the response to stimulation and detected by neural stimulation, or sleep deprivation), administration of modafinil to cats caused a sharp activation of the gene c-Fos in the anterior hypothalamic nucleus and the surrounding areas and weak in the suprachiasmatic nucleus, and the minimum gene activation in other areas such as the cerebral cortex or striatum. This activation of the hypothalamic-point was visible everywhere, in the process was involved and the amygdala. Studies in humans have shown clear differences between human exposure to modafinil, and amphetamine. In contrast to the effects of amphetamine or methylphenidate - excessive cheerfulness (which indicates a widespread neuronal activation), modafinil is selectively affects: the hypothalamus and amygdala.

Neurology
dopaminergic effects
Modafinil can increase the extracellular levels of dopamine in the prefrontal cortex of rats and in the caudate nucleus in dogs. Modafinil worked on dopamine and noradrenaline receptors (in the striatum) and the absence of such effects in mice has been linked with the disappearance of the effects associated with sleep, which confirmed the fact that the mechanism of action of modafinil really affects sleep. Recent research has shown the lack of influence of modafinil on the dopaminergic system, which may be associated with lower dosage used previously.

andrenergic impact
The invigorating effect of modafinil significantly weakened adrenergic receptor antagonists (group alpha and beta), but inhibition of the synthesis of catecholamine alpha-methyl-paratirozin does not diminish the impact.

Orexin-ergic effects
People deficient orexin (narcoleptics) modafinil shows good results, directly affecting the orexin neurons. This effect has the greatest impact on deficient mice, the effect of modafinil on the orexin system of healthy animals and humans is unknown. 3.5. Sedative and stimulating effect negative results of some studies about the effects of modafinil during the intentional deprivation of sleep, because the effect of 300 mg of modafinil during sleep deprivation is equivalent to receiving 20mg D-amphetamine. However, it was noted that the deterioration of self-control (the ability to accurately assess themselves and their surroundings) changes in the overconfidence (incorrect assessment of what is really capable of). The studies lasted for 64 hours (two nights without sleep) with a single dose of modafinil every 15 hours. Admission modafinil before sleep can seriously alter the sleep cycle and lead to subsequent lethargy, and can also cause side effects (worsening of mood and mental abilities). Recurrent hypersomnia - a phenomenon in which after the expiry of drugs against sleepiness sleepy more than to receive them. In contrast, preparations based on amphetamine modafinil not causes the phenomenon in cats, rats and mice. People who do not sleep for 64 hours and taken modafinil, this phenomenon also seen, in contrast to results with D-amphetamine reception. Modafinil does not cause recurrent hypersomnia. Exacerbation of attention observed in sleep deprivation for 10-12 hours after a single dose of 300 mg of modafinil, which is equivalent to 20 mg of D-amphetamine. The dose of modafinil 300mg of sleepiness is equivalent to 20 mg of the second dose of D-amphetamine. Brain sleep cycle is a balance of "ascending activating system" consisting of activating neurotransmitters (catecholamines, acetylcholine, orehina and so on.) And neurotransmitters (GABA, galanin), which inhibit the stimulation and promote sleep. Changing levels of activation and suppression of neurotransmitter generates a unique series of "switch-breaker." In general, regulation loop of vivacity and rest depends on the one hand, the circadian biorhythm from caused suprahiazimatic core and on the other - on the homeostatic need for sleep, which occurs during wakefulness. Modafinil is able to communicate with various stimulatory systems including serotonergic, noradrenergic, dopaminergic, glyutaminergic, histaminergic, oreksinergic and GABAergic pathways. While some studies modafinil used in the treatment of several other diseases and found that the side effect of insomnia lasted longer than in the placebo group, and Modafinil, adopted before bedtime, sleep did not give the participants of the experiment. Admission modafinil promotes mental stress.

The memory and thought processes
In healthy people, when receiving 100-200 mg of modafinil for 2 hours before the test (arithmetic test) improved storage properties, visual-spatial scheduling and rate of reaction. Short-term memory and accuracy of information processing improved after taking 200 mg of modafinil. In addition to the above, improvements are observed in the performance of tasks in general - increased motivation, enjoyment of the work done. In methamphetamine-dependent cognitive impairment dose of modafinil in a 400 g split into 3 days, can improve the properties of the short-term memory, which previously was not possible, however, a single dose of 200 mg of modafinil is not able to cause such effects.

Effects on appetite
Researchers condemning drug abuse is sometimes reported as a side effect of appetite in 16% (164cheloveka). Some researchers believe that this fact cause weight loss within one week, but no statistically.

Addiction
Modafinil is not able to activate the neural pathway that occurs in dependence, and is therefore considered that the drug has a relatively low threshold addiction other similar drugs. It is unlikely that modafinil will be used as a drug among addicts. Modafinil can help ease the breaking in methamphetamine-dependent, alcoholics and addicted to gaming, but the impact of the effect varies. Modafinil also reduces impulsivity drug-addicted, but this effect has effect only with subjects whose threshold impulsivity before experiments was already at a low level.

The impact of the Modafinil drug on people with certain diseases
multiple sclerosis
Disposable reception armodafinil (250 mg), patients with multiple sclerosis showed improvement mnemonic play, this effect was comparable to the placebo effect, but the fatigue, the ability to focus and speed of information processing the drug had no effect.

Precautionary measures. Toxicology
Tests revealed the following adverse effects of the drug - headache, dizziness, urine output, heart palpitations, tachycardia, anxiety, nervousness, gastrointestinal problems such as nausea and dry mouth, and abdominal pain. Apart from the above, modafinil is considered to be well-tolerated drug. Common side effects of modafinil include insomnia and decreased appetite.

Modafinil side effects
Side effects of modafinil, usually associated with stimulation of the central nervous system and may include nervousness, insomnia, tremors, euphoria, excitement and personality changes. The drug can also cause gastrointestinal symptoms such as nausea, vomiting, abdominal pain, dry mouth, anorexia and headache. Also, there may be high blood pressure, heart palpitations or abnormal heart rhythm. In rare cases it may occur an allergic rash, increased alkaline phosphatase, or in violation of the voluntary movements.

Availability:

Modafinil is currently to be found in more than two dozen countries. The drug, however, are not particularly popular on the black market and is not profitable target for counterfeiting. Modafinil available on medical prescription.

Armodafinil

Armodafinil (trade name Nuvigil) is enantiomerically pure form of a substance that promotes wakefulness, or evgeroika, modafinil (Provigil). It consists only of (-) - (R) enantiomer of racemic modafinil. Armodafinil manufactured by the pharmaceutical company Cephalon Inc. and it has been approved by the Food Safety and Drug Administration USA (FDA) in June 2007. Despite the fact that the two substances have similar half-lives, armodafinil reaches its peak concentration in the blood later than modafinil that can make it more effective as a substance promoting wakefulness in patients with excessive daytime sleepiness.

Systematic (IUPAC) name: (-) - 2 - (the R) - (diphenylmethyl) sulfinyl) acetamide
Trade names: Nuvigil
Category drugs in pregnancy: C
Dependence: Low
Methods of application: oral
Legal status: US: List IV; ℞ (released only on prescription)
Metabolism: liver, including CYP3A4 and other ways
Biological half-life: 12-15 hours
Excretion: urine (as metabolites)
Formula: C15H15NO2S
Molar mass: 273.35 g • mol-1

Medical applications of Armodafinil
Armodafinil currently approved by the FDA for the treatment of excessive daytime sleepiness associated with obstructive sleep apnea, narcolepsy and shift work. It is widely used off-label for the treatment of attention deficit hyperactivity disorder, chronic fatigue syndrome, and major depressive disorder. It has been shown that it improves alertness in the air traffic controllers.

Sleep disturbances
Armodafinil approved by the US FDA for the treatment of narcolepsy and sleep disorders associated with shift work, as well as in the adjuvant treatment of obstructive sleep apnea. For the treatment of narcolepsy and obstructive sleep apnea, armodafinil taken once daily at a dose of 150 mg or 250 mg in the morning. For the treatment of sleep disorders associated with shift work, armodafinil take a dose of 150 mg for one hour before the operation. Dose titration is required to mitigate some of the adverse effects. Please pay attention to Phenazepam.

Research of ArmodafinilSchizophrenia

In June 2010, it was revealed that the study armodafinila phase II as adjunctive therapy in adults with schizophrenia could not meet the primary endpoint, and clinical program was later discontinued. However, a study published in the same year, showed that patients with schizophrenia treated with armodafinil observed fewer negative symptoms of schizophrenia.

Jet lag
March 30, 2010 FDA declined to approve the use of Nuvigil for the treatment of jet lag disorder.

Side effects of Armodafinil
In the placebo-controlled studies, the most commonly observed side effects were headache, dry mouth, nausea, dizziness and insomnia. Possible side effects include depression, anxiety, hallucinations, euphoria, excessive activity and talkativeness, loss of appetite, tremors, thirst, rash, suicidal thoughts and aggression. Symptoms of modafinil overdose include trouble sleeping, anxiety, confusion, disorientation, sense of excitement, mania, hallucinations, nausea, diarrhea, strong acceleration or slowing heartbeat, chest pain and high blood pressure.

Pharmacology of Armodafinil
Pharmacodynamics
The mechanism of action is unknown Armodafinil. Armodafinil (R-modafinil) possesses pharmacological properties almost identical modafinil (a mixture of R- and S-modafinil). R- and S- enantiomers exhibit similar pharmacological effects in animals. Armodafinil is a drug, promoting wakefulness, similar to sympathomimetic substances, including amphetamine and methylphenidate, although its pharmacological profile is not identical to sympathomimetic amines. Armodafinil is an indirect dopamine receptor agonist; it binds in vitro to the dopamine transporter and inhibits dopamine reuptake. In modafinil, this activity has been associated in vivo with increased levels of extracellular dopamine. In mice, created by genetic engineering, and lacking the dopamine transporter (DAT), modafinil showed no activity associated with an increase in waking hours, suggesting that this activity is a DAT-dependent. However, the stimulatory effects of modafinil, unlike amphetamine, not counteract the effects of dopamine antagonist haloperidol receptor in rats. Additionally, alpha-methyl-p-tyrosine, dopamine synthesis inhibitor, blocks the effects of amphetamine, but does not block the locomotor activity induced by modafinil. In addition to the stimulating effects and the ability to increase locomotor activity in animals, according to the leaflet from Nuvigil drug armodafinil produces psychoactive and euphoric effects, changes in mood, perception, thinking and feelings typical of other stimulants of the central nervous system (CNS) in humans . Armodafinil as racemic modafinil, may also have reinforcing properties, as evidenced by his self-administration in monkeys previously taught to use cocaine. Armodafinil also partially considered a stimulant. Research company Cephalon, in which patients were given modafinil, methylphenidate and placebo showed that modafinil produces "psychoactive and euphoric effects and feelings similar to methylphenidate."

Pharmacokinetics
Armodafinil has a linear time-independent kinetics after single and multiple oral dose. The increase in systemic exposure proportional to the dose range of 50-400 mg. No time-dependent changes in kinetics were observed after 12 weeks of dosing. Homeostasis for armodafinil is developed within 7 days of dosing. At steady state, the systemic exposure armodafinil is 1.8 times larger than the effect after a single dose. concentration profiles for R-enantiomer of time after a single dose of 50 mg or 100 mg Nuvigil Provigil (modafinil, 1: 1 mixture of R- and S-enantiomers) are almost aligned. Nevertheless, the average armodafinil maximum concentration at steady state was 37% higher after administration of 200 mg Nuvigil, than the corresponding value of modafinil after the administration of 200 mg Provigil through more rapid excretion S-enantiomer.

Absorption
Armodafinil readily absorbed after oral administration. The absolute oral bioavailability was not determined due to the aqueous insolubility armodafinil that precluded intravenous administration. Peak plasma concentration is reached after about 2 hours on an empty stomach. Effect of food on the bioavailability of total armodafinil considered to be minimal; however, the time to reach peak concentration may be delayed for 2-4 hours when taken with food. Since the time to maximum concentration and delay associated with increased plasma concentrations later in time, food intake could potentially affect the onset and course of the pharmacological action of a temporary armodafinil.

Trade marks of Armodafinil
Armodafinil sold under a wide variety of brands worldwide.

R-Modawake - India
Artvigil - India
Waklert - India (discontinued Armod, Armod)
Nuvigil - US
Neoresotyl - Chile

Selank

Pharmacological group: tranquilizers

Pharmacological action Selank - a synthetic peptide analogue of the endogenous tafttsin has neurospecific original mechanism of action on the central nervous system and binds to specific receptors on the membranes of nerve cells. It has impact on the exchange of monoamines in the emotional structures of the brain (hypothalamus, diencephalon, the neocortex) and the activity of the brain enzyme tyrosine and tryptophan hydroxylase. Shows tropism to serotonergic system, normalizing the level of serotonin in the brain in experimental conditions caused its decline. Selank stabilizes the processes of excitation and inhibition in the brain and increases the resistance of neurons in the cerebral cortex to the functional load of high intensity. The pharmacological action of the drug spectrum dominated anxiolytic (anti-anxiety) effects by stimulating (activating) component. The drug does not possess hypnotic-sedativeand muscle relaxant properties. Positive effect on the mnemic and cognitive functions of the brain, including in their violation. Activates the processes of learning, memory, analysis and reproduction of information, improves parameters of attention and short-term memory. Improves stability and motivational value of adaptive behavior. Selank has Wegetotropona effect, improves vegetative maintenance of activity in conditions of emotional stress has an impact on optimizing adaptive reserve of the body. Selank is not detect unwanted side and toxic effect at 200-300-fold increase in dose. There has embryotoxic, teratogenic, allergenic, local irritating action does not detect the mutagenic properties. In preparation No adverse long-term effects. Selank not cause drug dependence phenomena. Selank absolute bioavailability when administered intranasally is 92.8%. The drug is rapidly absorbed from the nasal mucosa and after 30 seconds, detected in blood plasma. plasma concentration decreases progressively during 5-5.5 minutes. Metabolites by intranasal route of administration is not detected. It penetrates into the brain tissue. The drug is rapidly distributed to organs and tissues, it is found in unchanged form in a well-vascularized organs (liver, kidney, heart). The daily urine is not determined by any of unchanged drug or metabolites, that is caused by the rapid degradation under the influence of tissue Selank peptidase. Selank - synthetic heptapeptide analogue of the endogenous tetrapeptide tuftsin, with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. Selank sometimes called tuftsin analogue 7. tuftsin Victor Najjar was opened in 1969 (Siemion and Kluczyk, 1999). It produced mainly in spleen and part of the gamma immunoglobulin (IgG). Selank was first synthesized in Russia, when scientists tried to find a version - "superagonists" tuftsin. Selank effects can be divided into two broad categories: neurological and immune-modulating, the first group is associated with exposure to Selank brain derived neurotrophic factor (NBF) and the regulation of conservation enkephalins, and the second reflects a stimulating effect on the immune system Selank cells: phagocytes, neutrophils and others. Selank has anxiolytic, neurotrophic, nootropic, antidepresivnoe, antibacterial and anticancer activities in laboratory and natural conditions, is considered to be a promising agent for the treatment of various acute and chronic diseases. Although the action Selank considered in two categories, the new emerging area of scientific knowledge, called "neuroimmunology" provides a new explanation of the impact of immunomodulators in memory, cognition and behavioral responses.

Glossary
Pro-Gly-Pro, Gly-Pro and Pro-Gly - Eastern European term for the biological family of peptides, which contain all the members of glycine and proline, and affect gastric tissue and contribute to the formation of collagen; It refers to drugs or peptides, which are present in the chain addition Gly-Pro.
Heptapeptide - peptide whose structure contains seven amino acids.
Semax, also known as ACTH (4-10) - a synthetic analogue of the conjugate Gly-Pro ACTH with the structure of MET-GLU-HIS-PHE-PRO-GLY-PRO, is sometimes compared by exposure to Selank.
The growth factor - biological signaling hormone that promotes the growth, reproduction and cell division.
Neuroprotective drugs - are drugs, when administered to cause rapid and / or improve the long-term memory, learning ability, learning and cognitive function.
Neurotrophic drugs - drugs that cause an increase in the size, quantity, or other changes in the type of neural cells; growth factor that acts on the nervous tissue.
NBF - brain-derived neurotrophic factor
Enkephalins - two endogenous peptide (in the form of Leu and Met) binding to delta opioid receptors (in contrast to the action of receptors in Mu-endorphin)
Chemotaxis - the directed movement of cells or cell factor often used to refer to immune action (chemotaxis of leukocytes, neutrophils, macrophages, phagocytes, etc.)
Oligopeptide - peptide whose structure contains 20 or fewer amino acids.
Neuropeptide - locally producing peripheral or peptide which interacts with neural tissue, usually with the neuron.
Neuroimmunology - evolving discipline that studies the relationship between the immune and nervous systems.
Delta-opioid receptors - the receptors for which natural ligands are enkephalins (ligand - atom, ion or molecule is associated with a certain center); have antidepressant effect, involved in the regulation of NBF, cause cognitive improvement, reduce pain, are the protectors of the heart.
Immunoglobulin G (IgG) - protein complex isotopes antibodies consisting of four peptide chains: two heavy and two light located in «Y» -shaped form. IgG is the most common isotype antibody in circulation; It binds pathogens and affects various immune mechanisms.

Structure of Selank
Tuftsin and Selank are different from that present three smaller peptide in its chain. Adding PRO-GLY-PRO makes Selank Gly-Pro: it is more stable for circulation, has a large circulation, resistance to degradation, and greater ability to penetrate into the fabric:
"Useful properties of these compounds, suggesting their possible use as potential therapeutic agents linked to their performance and higher efficiency compared with tuftsin taken separately. (Dzierzbicka et al., 2005). " According to the patent (Goldstein et al., 1992), at a low concentration aqueous solution tuftsin loses biological activity, but chemical or structural integrity, remains unchanged. Selank was part of the intranasal preparations with a concentration of 0.15%, but is effective at lower concentrations, which has been proven in animal experiments in vivo.

Physiological function of Selank
The breadth and diversity of action and Selank tuftsin is best understood in the light of new knowledge about the body. Simon in his review, 2005 "The peptide-molecular bonds between the central nervous system and the immune system," writes: "The central nervous and immune systems for many years were considered independently. Now mutual relations between them have been proved and, as a rule, recognized by most scientists. These connections are realized mainly by various immuno- and neuropeptides. " It is both an immunomodulator and neuropeptide tuftsin Selank and provide new knowledge about the links between these systems. Mück writes about immunomodulatory effects tuftsin in cases of acute bactericidal shortages (eg after surgery), speaking also on its anti-tumor, anti-inflammatory and therapeutic effects (for example, in cases of immune disorders), "Action tuftsin is mediated by specific receptors on the surface of cells [white blood cells and macrophages ]. its anti-tumor activity both in vitro and in vivo has been demonstrated. The operation of tuftsin is its effect on metabolic processes in the basic cell (fosfoglyukonatny cycle; protein A and G, the distribution of Ca ++, redox reactions). These features, coupled with tuftsin low toxicity determine its usefulness for immunotherapy (Mucke, 1984). " Production of cytokines (information peptide molecules) in the cells of the body is the cause of certain inflammatory processes. Neuropeptides, which are not produced by nerve cells in the peripheral tissues, provide feedback to the nervous system (Villiger, 1994).
Villiger (1994) writes: "It is an expression that is the synthesis and secretion of neuropeptides immune system cells or connective tissue cells was recognized only recently ... rapid accumulation of knowledge about the natural metabolism of these highly reactive substances point to new therapeutic possibilities in the field of Neuroimmunology." Immune and nervous systems can operate independently to modulate inflammatory processes by means of various mechanisms, recent studies also indicate that they can modulate inflammation "additive, synergistic or antagonistic" (Villiger 1994).

Research and development of Selank medicines
The study of the relationship between the immune and nervous systems, provides new opportunities for the understanding of diseases such as chronic fatigue syndrome, Lyme disease, lupus, Crohn's disease and other immune disorders affecting the nervous system. It also offers new opportunities for improvement of brain activity by the use of drugs to prevent the degradation of enkephalin or regulatory NBF that can provide an antidepressant effect, help to improve memory and prevent the decline of cognitive capacity during aging. . Kost et al write "has been demonstrated dose-dependent effect when exposed to synthetic Hecto-peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) and Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) to enkephalin -destroy human serum enzymes. Inhibitory effect of Semax (at IC50, or concentration of half-maximal inhibition of 10 .mu.M) and Selank (IC50 20 .mu.M) is more pronounced than that of puromycin (IC50 10 mM), bacitracin, and some other substances. Furthermore Hecto-peptide their pentapeptide fragments also possess inhibitory activity ;. tri-, tetra- and hexapeptide fragments did not show such effect. As described above enzymes are involved not only in the degradation of enkephalins, and other regulatory peptides, one can assume that one of the mechanisms of biological activity Semax and Selank is their inhibitory activity. " According Nagahara and OE, such modulators NBF as Selank, able to draw age-related cognitive changes, by preventing atrophy, improve cell signaling and gene expression in adults, providing a protective effect on neural circuits involved in the development of Alzheimer's disease: "In old rats infusion NBF is able to draw cognitive impairment, improve age-related changes in gene expression and restore cell signaling. In adult rats and primates, NBF prevent damage caused by the loss of entorhinal cortical neurons. Older primates NBF changes the state of neuronal atrophy and improves age-related cognitive impairment. Taken together, these results indicate that NBF has significant protective effects on participating in the development of Alzheimer's disease the most important neural circuits, through amyloid-independent mechanisms. NBF possible therapeutic use as a potential therapy for Alzheimer's disease (2009). " Selank Exposure to cytokines such as interleukin apparently varies depending on conditions, therefore, immune factors increase its activity in certain situations, that provides bactericidal or antitumor effect and inhibiting others. Thus Selank can be used as a drug for treating inflammatory neurological disorders of immunity, such as multiple sclerosis and other immune disorders, such as progressive primary hypothyroidism. . Basin and others have shown that the use of tuftsin improves the condition of animals with experimental autoimmune encephalomyelitis (EAE), multiple sclerosis, "Introduction tripeptide macrophages / microglia inhibitory factor and tetrapeptide macrophages / microglia-stimulator tuftsin attenuated symptoms of EAE. Dates of activation of macrophages / microglia are critical to the clinical results of EAE. It has been proven that it is possible to prevent progression of the disease in its early stages when changing the timing of the activation of microglia, which, in turn, alter the systemic immune response to the activation of helper 2 genes of T-cells, which help to restore the body after EAE (2007). " Compounds Selank or tuftsin offer new opportunities for administration in connection with what are connected on a molecular level, or enclosed in a liposome system, other drugs such as Azidozimidin (HIV / AIDS) may act on particular cells, which would otherwise difficult to achieve: «IgG-immunomodulatory peptide tuftsin, Thr-Lys-Pro-Arg, is easily recognizable by specific receptors on phagocytes, such as macrophages and their ability to direct the proteins and peptides in these regions. In order to deliver the 3'-azido-3 '-dezoksitimidine (Azidozimidin) in HIV-infected macrophages was synthesized from compound Azidozimidin tuftsin. This compound has characteristic features of both components. As Azidozimidine, it inhibits the activity of reverse transcriptase and HIV-antigen expression, and as tuftsin stimulates IL-1 release from macrophages in mice and increases the immunogenic cell function. Importantly, the compound is not cytotoxic for T-cells. These results indicate that the compound Azidozimidin-tuftsin may have potential in the treatment of AIDS. Selank may offer additional advantages over tuftsin in connection with its gliproglinic structure due to faster and longer and deeper systemic effects, the connection is PRO-GLY-PRO. According to Lucas et al., Tuftsin and its analogues were tested for in vitro efficacy for the treatment of systemic lupus erythematosus (SLE), and indicators showed improved immune response and mobility in patients. Researchers predict improvement in forecasts, the reduction of disease progression and improve control of infections in people with SLE: "The main endogenous tetrapeptide beams and 6 analogs were examined in the laboratory for examination of their stimulatory capacity at the chemotaxis of monocytes in patients with SLE ... Efficiency tetrapeptides chemotaxis also stimulated phagocytosis and random migration of monocytes, although to a lesser degree. Also discussed were the structure-activity relationships and the influence of the clinical stage of the disease. Experimental evidence leads to a favorable outlook for the immunotherapeutic value of these oligopeptides in the fight against infections and progress in the disease in patients with SLE. (1984) ".

Special arrangements anxiolysis: enkephalin preservation
Sokolov et al write:
"A comparative study of the activity of enkephalin-depleting plasma enzymes in open field trials in mice with different phenotypes of emotional and stress reactions showed that Selank at a dose of 100 mg / kg [human equivalent dose of 17 mcg / kg] produces an anxiolytic effect and increases the period of plasma half-life leu-enkephalin ... that is associated with inhibition of enzymes that reduce the level of enkephalin. Impact Selank behavioral responses and plasma activity of enzymes that destroy enkephalin in mice with different phenotypes of emotional and stress reactions. (Sokolov et al., 2002). "
Guidelines for the diagnosis of mental disorders and the statistics diagnosed patients experiencing anxiety or phobia, who has been seen reduced total enkephalin activity, as well as the weakening of the half-life entsefalina:
"Heptapeptide Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), which weakens the behavioral responses of anxiety and does not cause side effects typical of the majority of drugs, dose-dependently inhibits the enzymatic hydrolysis of enkephalin plasma (IC50, or concentration of half-maximal inhibition is 15 pM). Selank considered more powerful than the peptidase inhibitors bacitracin and puromycin in suppressing enkefalinazisa. The results indicate that high efficiency in the treatment Selank anxiety and phobic disorders, including generalized anxiety, related to its ability to inhibit the enkephalin hydrolysis. (Zozulya et al.). "
It is assumed that the inhibition of enzymes, reducing the level of enkephalins - Selank independent action in relation to the immunomodulatory processes, but epidemiological studies of increased cases of depression or anxiety after injury, often accompanied by a decrease in the activity of the immune system and increase the likelihood of infection, deserve further evaluation of dual effects tuftsin / Selank. This may lead researchers to consider Selank or similar peptides as dual use of antidepressants with favorable immunomodulatory properties.
Double action Selank associated with both the modulation of the immune response, and with the improvement of cognitive parameters may make it an attractive destination for persons suffering from acute injuries.

NBF, injury, insomnia, and Neuro-topia
One of the links connections between immune and endocrine systems is immune and endocrine response as a result of sleep deprivation, which also is inflammatory in nature:
"The links between the immune and endocrine systems are another important point in relation to which cytokines affect sleep and, on the contrary, sleep and related processes, including changes in neurotransmitters and neuronal activity, can affect the level of cytokines. The ability to improve sleep for release and / or production of certain cytokines ... may indicate an increase in sleep-related activity of specific immune system. Furthermore, in humans after the primary response to antigens by increased sleep subsequent viral challenge. In animals, the results are less consistent and focused on secondary aspects. Sleep-related cytokine levels may be mediated by modulation of the endocrine parameters. (Marshall and Bourne, 2002). "
Selank promotes the formation of memory neurons, reduces inflammation, modulate endocrine (and paracrine) factors related to the immunological and neurological changes and improves the results in case of injury. In addition, indirectly through NBF-controlled action Selank it demonstrates the same properties as that of conventional antidepressants:
. Russo-Neustadt and others write that:
"These results suggest the possibility that increased expression NBF may be important in the treatment of antidepressants. Expression induction treatment for NBF activity / pharmaceutical combination is understood as an important tool for further study as a potential drug for the treatment and management of depression. (2001) ".
Garcia et al. Note that "a large body of evidence has established the link between stressful life events and the corresponding development or worsening of depression," and then proceeds to establish a link between the disabled responses to environmental stimuli, cognitive decline and memory functions, as well as metaplastichnosti decline. "
Garcia et al. Write that "in response to the stress and depression of neurons atrophy and loss of cells" (2001). Regulation of NBF, and possibly other mechanisms that modulate neurotrophic growth factor, are another mechanism Selank offering the advantage in post-traumatic or depressed state of the patient. Neurogenesis, as well as the prevention of neuronal loss are related to this mechanism (2001).
Waldman and OE, parameters studied when exogenous tuftsin "unavoidable stress" and found that at doses of 20-250 mg / kg was observed behavioral effect of reducing the time and increasing the time of immobilization of the active phase (rats were divided into groups, one of which was Enter the 6-hydroxydopamine, disruption agent terminals catecholamines and the other not; the first was called "unemotional" one and the second "emotional"), which is mediated by catecholaminergic activity, coupled with tyrosine hydroxylase, which correlates the effectiveness of antidepressants and stimulants in humans.

Nootropic effects of Selank
Mechanisms established anxiolytic (anti-enkephalinases) and the antidepressant (NBF-regulation) Selank effect, can be used to improve brain health. Semenova et al. Assigned tuftsin and its analog in rats by injection (300 mg / kg, which is equivalent to 50 mg / kg in humans) and showed a significant gain in research activities, as well as stimulating and preventive effect, reducing anxiety and antidepressant effects, improving skills learning and memory:
"It was found that the appointment of the peptides increases the desire to research activity in rats. TP-1 Active influence continued for 6 hours. Daily administration tuftsin or TP-1 for 15 min before the experiment facilitated training and stabilized the conditioned responses to food reinforcement. Experimental animals reacted to emotionally negative influence is much weaker than the controlled, which is caused by a sharp reduction in control over the amount of food reinforcement. (1988) ". In a later work (2010), Semenov has demonstrated long-term (30 days) the possibility of the appointment Selank animals, with the changes marked in the metabolism of serotonin, a reaction to the food reward and memory consolidation:
"Effects Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), is a synthetic derivative of the endogenous tetrapeptide tuftsin, training and processes associated with memory, and metabolism of serotonin (5-HT) have been experimentally investigated on Wistar rats. The animals were trained in using food rewards, and spent 30 samples per day. After the 10th study began Selank administered (300 mg / kg) or saline. Development of a conditioned reflex to the food reward was continued 30 minutes later. Animals were tested after 24 hours, 7 and 30 days after treatment. Selank activated single injection of serotonin metabolism in the hypothalamus and brain caudal epididymis from 30 minutes to 2 hours. It was found that Selank induces an increase in the storage stability of 30 days. These results provide direct evidence that Selank entered during the consolidation phase, can improve memory processes. Selank nootropic activity, probably due to its obvious influence on the levels of serotonin and its metabolites in the brain. "
The authors express greater confidence in the designation Selank as "nootropic" in connection with demonstrated improvements in testing procedures, longer and more time-bound action. The metabolism of serotonin also provide additional physiological basis for the antidepressant effect Selank.

Availability of Selank
Selank used for anxiety and anxiety-asthenic disorders, appropriate diagnostic criteria for generalized anxiety disorder; neurasthenia; adaptation disorders. The drug prescription.

Mildonium

Mildonium (INN), trademarks Mildronat, Mildronāts, also known as Quaterine, Met-88 and THP - is the limited availability of the pharmaceutical drug market, designed in 1970 and manufactured by Ivar Kalvins first Latvian company Grindeks and some generic manufacturers. It is distributed in Eastern European countries as a medicine against ischemia. From 1 January 2016, the drug included in the list of the World Anti-Doping Agency of substances (WADA) prohibited for use by athletes. However, there is controversy about its use as a substance enhancing athletic performance. Some athletes are known to have used it before it was banned.

Systematic (IUPAC) name: 2- (2-carboxylate ethyl) -1,1,1-trimethylhydrazinium
Trade names: Mildronate
Number CAS 86426-17-7
Synonyms: THP, MET-8 Mildronāts or Quaterine
Formula: C6H15N2O2 +
Molar mass: 147.19 g / mol
Solubility in water:> 40 mg / mL mg / mL (20 ° C)

Medical use of Mildonium

Mildonium used in medicine for the treatment of angina and myocardial infarction. The first clinical trial of the effectiveness of using a combination of Mildonium and lisinopril, angiotensin converting enzyme inhibitor, for the treatment of chronic heart failure, was conducted in 2005. The test showed that the combination of lisinopril and Mildonium can improve the quality of life, exercise tolerance, as well as mechanisms of peripheral blood circulation in patients with chronic heart failure. Another research report in 2008 showed that the combination of lisinopril and Mildonium improved baroreceptor reflex in patients with chronic heart failure patients. In February 2010, a further clinical trial examining only patients with angina, tested the efficacy and safety of Mildonium in conjunction with standard measures to improve exercise tolerance. The study found that the drug significantly improved exercise capacity in stable patients with angina. Team of the Fourth Military Medical University, Xi'an, Shaanxi, China, conducted a clinical phase II trial involving 227 patients for efficacy and safety Mildonium in acute ischemic stroke, which was completed in August of 2013. The study authors concluded that Mildonium was as effective and safe as sinepazide injection.

Pharmacology of Mildonium
Mildonium inhibits oxidation of fatty acids, presumably by inhibiting the enzyme gamma-butyrobetaine hydroxylase Carnitine in the biosynthetic pathway. γ-butyrobetaine hydroxylase belongs to the superfamily of 2-oxoglutarate and oxygenase catalyzes the formation of L-carnitine from gamma-butyrobetaine. Despite the fact that the initial data suggest that Mildonium is non-competitive and not hydroxylated analogue of gamma-butyrobetaine, further research revealed that Mildonium is a substrate for the gamma-butyrobetaine dioxygenase. X-ray analysis and in vitro biochemical studies indicate that communicates with the pocket Mildonium substrate γ-butyrobetaine hydroxylase and acts as an alternate substrate, and therefore a competitive inhibitor. Typically, the action of this enzyme on its substrate and γ-butyrobetaine gives 2-oxoglutarate in the presence of additional oxygen substrates L-carnitine products, succinate and carbon dioxide; in the presence of an alternative substrate reaction produces semialdehyde malonic acid, formaldehyde (similar to the action of demethylases histones), dimethylamine and (1-methyl-imidazolidin-4-yl) acetic acid, "unexpected product with extra carbon-carbon bond, the resulting N demethylation coupled with oxidative rearrangement probably unusual via a radical mechanism. " In this unusual mechanism is probably involved regrouping Stephen. Inhibition meldonium γ-butyrobetaine hydroxylase gives the value of half-maximal inhibitory concentration (IC50) 62 micromolar, that other authors of the study described as "potent." Mildonium is an example of an inhibitor which acts as simulant non-peptidyl substrate. The other primary study showed reports (nuclear magnetic resonance), which also binds to Mildonium acetyltransferase carnitine, a ubiquitous enzyme that plays a role in cellular energy metabolism; it also inhibits this enzyme, although slightly more (the inhibition constant, Ki, 1,6 mmoles).

Physical and chemical properties of Mildonium
Chemical name Mildonium - 3- (2,2,2-trimethyl-Imil hydrazinium) propionate. This substance is a structural analog of gamma-butyrobetaine with amino replacing C-4 methylene γ-butyrobetaine. γ-butyrobetaine is a precursor in the biosynthesis of carnitine.

Society and Culture
dope
Mildonium was added to the list of prohibited substances World Anti-Doping Agency (WADA), starting from January 1, 2016, due to evidence of its use by athletes to enhance performance. Mildonium was on the list of preparations for the WADA monitoring 2015. WADA classifies preparation as metabolic modulator, as well as insulin.

Victims of Mildonium
March 7, 2016, the former world champion tennis player and world number one Maria Sharapova announced that she failed a doping test in Australia due Mildonium detection. She said she took the drug for a decade to treat a variety of health problems, and did not notice that he was listed as banned. Earlier in the day, Russian figure skater Ekaterina Bobrova announced that it has also been tested positive on Mildonium at the European Figure Skating Championships in 2016. Bobrov was "shocked" by the results of the test, because she knew that Mildonium included in the list of banned substances, and avoid foods that contain banned substances. Other athletes who are temporarily forbidden to participate in the competition due to the use Mildonium - Swedish middle distance runner of Ethiopian origin Abeba Aregawi, Ethiopian long-distance runner Endeshaw Negesse, Russian cyclist Eduard Vorganov and Ukrainian biathletes Olga Abramova and Artem Tishchenko. World Anti-Doping Agency has recorded 110 positive samples with traces Mildonium in the period from January 1 to March 10.

Disputes about Mildonium
A study in December 2015, published in the «Drug Testing and Analysis» magazine says that Mildonium "shows an increase in performance and endurance in athletes, faster rehabilitation after training, protects against stress and improves the function of the activation of the central nervous system (CNS)» . The manufacturer, the company of Grindex, said he did not think that the use of Mildonium should be prohibited for athletes. The company said that the drug acts primarily by reducing cell damage that can be caused by some of the by-products of carnitine. Mildonium "is used to prevent ischemic cell death, and not to increase the performance of normal cells," the statement said. "Mildonium can not improve athletic performance, but it can stop tissue damage in the case of ischemia," that is, when there is insufficient blood flow to the heart. The drug was invented in the mid-1970s at the Institute of Organic Synthesis of the Academy of Sciences of the Latvian SSR Ivars Kalvins. Kalvins criticized the ban, saying that WADA did not provide scientific evidence that the drug can be used as doping. According to him, Mildonium does not improve athletic performance, and most have been used by athletes to prevent damage to the heart and muscles, caused by lack of oxygen during high-intensity exercise. He argued that not allowing athletes to take care of your health is a violation of human rights, and that the decision was taken or because of prejudice against athletes from Eastern Europe or in order to reduce competition in the competition. Liene Kozlovsky, head of anti-doping department of the Latvian Centre for Sports Medicine, has rejected the allegations that the ban is a violation of the rights of athletes, saying that Mildonium dangerous in large doses, and should be used only under medical supervision for the treatment of real health problems. She also suggested that the Russian athletes have not received adequate warning that the drug was banned due to the suspension of the anti-doping agency of the Russian Federation at the end of 2015. Forbes reported that a professor of anesthesiology Michael Joyner of the Mayo Clinic in Rochester, Minnesota, studied how people respond to the physical and mental stress during exercise and other activities, said that "there is insufficient evidence regarding the actions of many of the compounds that are expected improve athletic performance. Their use has something in common with urban legends, and it is unclear whether these products really effective. I would be shocked if he knew that this substance (Mildonium) has efficacy above caffeine or creatinine (a natural substance, which, if taken as a supplement, supposedly, helps to increase muscle mass). " Ford Vox, a doctor from the United States, specializing in regenerative medicine and journalist, said that "there is not much scientific evidence to support the use of this substance as an athletic performance booster."

Member approval of Mildonium
Mildonium that is not approved by the FDA in the United States, is a registered prescription drug in Latvia, Russia, Ukraine, Georgia, Kazakhstan, Azerbaijan, Belarus, Uzbekistan, Moldova and Kyrgyzstan.

Available forms of Mildonium
Mildonium sold in capsules in 250 mg and 500 mg, and a 10% Mildonium solution for injection.

Economy of Mildonium
Mildonium made of Grindex Company, the Latvian pharmaceutical company, which has offices in thirteen countries of Eastern Europe, as a means for the treatment of heart disease. Company identifies it as one of its main ingredients. In 2013, its sales amounted to 65 million euros.

Cyanocobalamin

Pharmacological group: Vitamins; Vitamin B complex

Pharmacological action: vitamer vitamin B12. In the body (primarily in the liver) is converted into methylcobalamin and 5-deoxy-adenosyl cobalamin. Methylcobalamin is involved in the conversion reaction of homocysteine to methionine and S-adenosylmethionine - key metabolic reactions pyrimidine and purine bases (and hence DNA and RNA). When vitamin deficiency in this reaction it may replace methyl-tetrahydro-folic acid, wherein the reaction folic acid needs for disturbed metabolism. 5 5-deoxy-adenosyl cobalamin serves as a cofactor for the isomerization of L-methylmalonyl-Cola in succinyl CoA - important reactions of carbohydrate and lipid metabolism. B12 vitamin deficiency leads to disruption of the proliferation of rapidly dividing cells of the hematopoietic and epithelial tissue, as well as to disruption of neuronal myelin sheath formation.
Molecular formula: C63H88CoN14O14P
Molar mass: 1355.38 g / mol
Appearance: dark-red solid
Melting point:> 300 ° C
Boiling point:> 300 ° C
Solubility in water: good

Cyanocobalamin is the most common and widely produced chemical compound having vitamin activity vitamin B12. Vitamin B12 - is the common name of any vitamer vitamin B12. Since the body is able to convert cyanocobalamin active compound in any B12, cyanocobalamin itself a form (or vitamers) B12, although largely an artificial joint. Cyanocobalamin is not usually found in living organisms, but animals can convert commercially produced in the active cyanocobalamin (cofactor) form of the vitamin, such as methyl cobalamin. Cyanide released in this process is so small that it is negligible toxicity.

Chemical properties of Cyanocobalamin
Cyanocobalamin is the most widely known and of vitamers produced vitamin B12 family (family of chemical compounds that function as B12 in the body), as the more stable cyanocobalamin is exposed to air to form B12. It is amenable to crystallization the easiest and hence most simply cleaned after production by bacterial fermentation or synthesis in vitro. It can be obtained in the form of dark red crystals or amorphous red powder. Cyanocobalamin is very hygroscopic in the anhydrous form and has a moderate solubility in water (1:80). It is resistant to sterilization in an autoclave for a short period of time at a temperature of 121 ° C. Coenzymes Vitamin B12 is very unstable to light. Animals cyanide ligand substituted with other groups (adenosyl, methyl), which represent the biologically active form. The remainder of the cyanocobalamin is unchanged.

chemical reactions
Cobalt central atom generally exists in the trivalent state, Co (III). However, when subjected to different reduction conditions cyanocobalamin central cobalt atom may be reduced to Co (II) or Co (I), which are commonly referred to as B12r and B12S respectively. B12S B12r and can be obtained from cyanocobalamin by controlled reduction or by chemical reduction using sodium borohydride in alkaline solution, zinc in acetic acid or by exposure to thiols. As B12r, and B12S are indefinitely stable in anoxic conditions. B12r in solution acquires an orange-brown color. With natural daylight B12S bluish-green color, and under artificial lighting - purple. B12S - this nucleophilic particles that make up the aqueous solutions and are often called "super-nukleofils". This feature allows you to create convenient preparations of cobalamin analogues with various substituents through nucleophilic attack on the deputy or unsaturated halogenated substituents. For example, cyanocobalamin may be transformed into analogues via reduction to cobalamins B12S, followed by addition of the corresponding alkyl halides, acyl halides, alkene or alkyne. Difficulties associated with sterols - is the main limiting factor in the synthesis of coenzyme B12 analogues. For example, there is no reaction between chloride and neopentyl B12S, a secondary alkyl halide analogues are too unstable to isolate. Studies suggest that this is due to the strong coordination between the benzimidazole and the central atom of cobalt, pulls it in the plane of the corrin ring. Trans-effect also determines the polarizability of communication Co-C. However, once separated from the cobalt benzimidazole when quaternization with methyl iodide, it is replaced by hydroxyl ions or H2O. Various secondary alkyl halides then easily attacked B12S modified to give the corresponding stable analogues of cobalamin. The products typically recovered and purified by phenol extraction or column chromatography methylene chloride. Cobalamin analogues obtained in this manner include natural and cobalamid coenzymes methylcobalamin as well as other cobalamins which do not occur in nature, for example, vinilcobalamin, and carboxymethylcobalamin , cyclohexylcobalamin. This reaction is currently being developed for use as a catalyst for chemical dehalogenation, the organic reactant and the catalyst system photosensitized.

Production of cyanocobalamin
Cyanocobalamin is commercially produced by bacterial fermentation. When fermentation of various microorganisms using a mixture of methyl, hydroxo and adenosylcobalamin. These compounds are converted to cyanocobalamin by adding potassium cyanide in the presence of sodium nitrite and heat. Since most species of Propionibacterium produces endotoxins or exotoxins and has GRAS status (i.e., is generally considered as Safe) in the US, it is currently considered the most preferred bacterial fermentation organisms to produce vitamin B12. Historically, a form of vitamin B12 is hydroxocobalamin is often produced by bacteria, and then, in the course of purification after separating the activated carbon from bacterial cultures and transformed into cyanocobalamin. The first extraction of vitamin B12 that change was not immediately understood. Cyanide is naturally present in the activated carbon, hydroxocobalamin and having a high affinity for cyanide, and creates its takes cyanocobalamin. Cyanocobalamin is found in most pharmaceuticals, since the addition of cyanide to stabilize the molecule. France provides 80% of world production of cyanocobalamin. In the year sold more than 10 tons of this compound, 55% of all sales come from animal feed, and the remaining 45% - for human consumption.

Pharmaceutical use of Cyanocobalamin
Cyanocobalamin is usually prescribed for the following reasons: after complete or partial surgical removal of the stomach or intestines, to provide an adequate level of vitamin B12 in the blood, for treatment of pernicious anemia; vitamin B12 deficiency due to its low income from the food; thyrotoxicosis; hemorrhages; cancer, liver and kidney. Cyanocobalamin injections often prescribed for patients with gastric bypass anastomosis, with bypass part of the small intestine, hinders the absorption of B12 from food and vitamins. Cyanocobalamin is also used in the Schilling test to identify a person's ability to absorb vitamin B12.

The end products of the treatment of cyanide poisoning
In cyanide poisoning cases, the patient is given hydroxocobalamin, cyanocobalamin predecessor. Hydroxocobalamin binds with cyanide ion and forms cyanocobalamin, which then can be released through the kidneys. Hydroxocobalamin has been used for many years in France and in December 2006 was approved by the FDA under the trade name Cyanokit.

Possible side effects of cyanocobalamin
Oral administration of cyanocobalamin may occur a number of allergic reactions such as hives, difficulty breathing, swelling of the face, lips, tongue, or throat. Less serious side effects may include headache, nausea, indigestion, diarrhea, joint pain, itching or a rash. In the treatment of certain forms of anemia (eg, megaloblastic anemia), the use of cyanocobalamin can result in severe hypokalemia, sometimes fatal (but the same effect is to be observed when taking any vitamer B12 is, not only cyanocobalamin). In the application of vitamin B12 Leber's disease patients may suffer from rapid atrophy of the optic nerve. Vitamin B12 forms for injections (such as hydroxocobalamin itself) is generally available as pharmaceuticals, and are the most frequently used injectable forms of vitamin B12 in many countries. cyanocobalamin injections are the most common forms of vitamin B12 injections in the United States.

Availability:
Cyanocobalamin is used for conditions involving a deficiency of vitamin B12. Dispensed by prescription.