|Systematic (IUPAC) name|
|Biological half-life||1 h (prodrug to modafinil; t1/2 is 12–15 h for modafinil)|
|Molar mass||289.351 g/mol|
|(what is this?)|
Adrafinil (INN) (brand name Olmifon) is a discontinued wakefulness-promoting agent (or eugeroic) that was formerly used in France to promote vigilance (alertness), attention, wakefulness, mood, and other parameters, particularly in the elderly. It was also used off-label by individuals who wished to avoid fatigue, such as night workers or others who needed to stay awake and alert for long periods of time. Additionally, "adrafinil is known to a larger nonscientific audience, where it is considered to be a nootropic agent."
Adrafinil is a prodrug; it is primarily metabolized in vivo to modafinil, resulting in very similar pharmacological effects. Unlike modafinil, however, it takes time for the metabolite to accumulate to active levels in the bloodstream. Effects usually are apparent within 45–60 minutes when taken orally on an empty stomach.
Adrafinil was marketed in France under the trade name Olmifon until September 2011 when the French Agency for the Safety of Health Products (AFSSAPS) reassessed the drug and proposed the withdrawal of marketing permission, citing known adverse reactions and insufficient evidence of efficacy for approved indications and hence an unsatisfactory risk–benefit ratio. Cephalon voluntarily discontinued the drug shortly thereafter. Adrafinil is unregulated in the United States and does not have Food and Drug Administration approval.
Adrafinil was discovered in 1974 by two chemists working for the French pharmaceutical company Laboratoires Lafon who were screening compounds in search of analgesics. Pharmacological studies of adrafinil instead revealed psychostimulant-like effects such as hyperactivity and wakefulness in animals. The drug was first tested in humans, specifically for the treatment of narcolepsy, in 1977–1978. Introduced by Lafon (now Cephalon), it reached the market in France in 1984, and for the treatment of narcolepsy in 1985.
In 1976, two years after the discovery of adrafinil, modafinil, its active metabolite, was discovered. Modafinil appeared to be more efficient than adrafinil in animal studies, and was selected for further clinical development, with both adrafinil and modafinil eventually reaching the market. Modafinil was first approved in France in 1994, and then in the United States in 1998. Lafon was acquired by Cephalon in 2001. As of September 2011, Cephalon has discontinued Olmifon, its adrafinil product.
Because α1-adrenergic receptor antagonists were found to block effects of adrafinil and modafinil in animals, "most investigators assume that adrafinil and modafinil both serve as α1-adrenergic receptor agonists." However, adrafinil and modafinil have not been found to bind to the α1-adrenergic receptor and they lack peripheral sympathomimetic side effects associated with activation of this receptor; hence, the evidence in support of this hypothesis is weak, and other mechanisms are probable. Modafinil was subsequently screened at a variety of targets in 2009 and was found to act as a weak, atypical blocker of the dopamine transporter (and hence as a dopamine reuptake inhibitor), and this action may explain some or all of its pharmacological effects. Relative to adrafinil, modafinil possesses greater specificity in its action, lacking or having a reduced incidence of many of the common side effects of the former (including stomach pain, skin irritation, anxiety, and elevated liver enzymes with prolonged use).
In a clinical trial with clomipramine and placebo as active comparators, adrafinil showed efficacy in the treatment of depression. In contrast to clomipramine however, adrafinil was well-tolerated, and showed greater improvement in psychomotor retardation in comparison. As such, "further investigations of the antidepressive effects of adrafinil are warranted."
Society and culture
In the United States, adrafinil is currently[update] unregulated. It has not been approved for any clinical uses by the U.S. Food and Drug Administration. Unlike modafinil, adrafinil is not classified as a controlled substance and does not fall under DEA jurisdiction; in particular, it is legal to possess without a prescription and can be imported privately by citizens.
"Adrafinil had been referred to the MCC for classification as a prescription medicine by the Medicines Control section of Medsafe following growing concern about increased imports and potential abuse of this substance as a party drug. Evidence of misuse was supplied in support of the request for classification.
Adrafinil is not scheduled in New Zealand but is chemically related to modafinil which is a prescription medicine taken orally for mental function impairment in the elderly.
All participants agreed that adrafinil should be classified as a prescription medicine."
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