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