Modafinil

Modafinil (sold as Provigil®, Alertec®, and Vigicer®) is a drug used to treat narcolepsy, made by the pharmaceutical company Cephalon. It is not a typical stimulant and is marketed as a "wakefulness promoting agent." more...

Indications

The manufacturer claims that modafinil allows people who suffer from unusual fatigue to remain awake without side effects or impairment of job performance. However it does not live up to this in all cases, occasionally producing rashes and intestinal problems. The usual prescription is for a single dose to be taken shortly after waking; its effects last for most of the day without preventing normal sleep at night, though in narcolepsy twice-daily administration is required. Under no-sleep conditions, a dose is taken at 8 hour intervals.

Dosage varies and the drug is more effective on patients who are using modafinil for the first time. The half-life in the human body is about 15 hours. Of the many side effects documented in double blind studies only headache was statistically significant at an increase of 5%, however a number of other side effects were about 1% higher than the placebo.

Modafinil is not indicated for complaints of lack of energy or fatigue; but it appears to be very helpful for some patients. Also, it has been used in the treatment of hypersomnia, a disorder in which patients lack the capacity for meaningful sleep and may require ten or more hours per day.

In January of 2005, researchers at the University of Pennsylvania published the results of a small study, which found that modafinil may help recovering cocaine addicts fight their addiction.

Clinical trials have suggested that modafinil may be effective for treatment of Attention Deficit Hyperactivity Disorder (ADHD). In November 2005, pharmaceutical company Cephalon received an approval letter from the US Food and Drug Administration (FDA) to market Sparlon (TM), a brand name of a tablet containing modafinil, for the treatment of ADHD in children and adolescents ages 6 through 17. Data from three clinical trials were submitted by the company to the FDA for evaluation as part of the approval process.

Pharmacology

The exact mechanism of action is unclear, although in vitro studies have shown it to inhibit the reuptake of dopamine. While co-administration of a dopamine antagonist mitigates the stimulant effect of amphetamine, it does not negate the wakefulness-promoting actions of modafinil. Modafinil activates glutaminergic circuits while inhibiting GABA. Modafinil is thought to have less potential for abuse than other stimulants due to the absence of any significant euphoric or pleasurable effects.

The central stimulating effect of modafinil shows dose and time-related features. The effect tends to be enhanced by chlorination but reduced by methylation. Modafinil blocks the reuptake of noradrenaline by the noradrenergic terminals on sleep-promoting neurons from the ventrolateral preoptic nucleus (VLPO). Such a mechanism could be at least partially responsible for the wake-promoting effect of modafinil.

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