Adrafinil, sold under the brand name Olmifon, is a wakefulness-promoting medication that was formerly used in France to improve alertness, attention, wakefulness, and mood, 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, the medication has been used non-medically as a novel vigilance-promoting agent. Reports of this side effect also exist for modafinil. hence, the evidence in support of this hypothesis is weak, and other mechanisms are probable. 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).
Pharmacokinetics
In addition to modafinil, adrafinil also produces modafinil acid (CRL-40467) and modafinil sulfone (CRL-41056) as metabolites, which form from metabolic modification of modafinil.
Chemistry
Adrafinil is the N-hydroxylated analogue of modafinil and is also known as N-hydroxymodafinil.
Analogues of adrafinil include modafinil, armodafinil, CRL-40,940, CRL-40,941, and fluorenol, among others.
Synthesis
A drugs of the future article was published on CRL-40,028: In addition there was a CNS review:
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The reaction of benzhydryl bromide [776-74-9] (1) with thiourea [62-56-6] (2) gives benzhydrylthiol [4237-48-3] (3). Alkylation with chloroacetic acid (4) gives so-called “benzhydryl-thioacetic acid”, i.e. 2-(benzhydrylthio)acetic acid [63547-22-8] (5). Fischer–Speier esterification with ethanol gives [63547-23-9] (6). Treatment with hydroxylamine gives [63547-44-4] (7).
History
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.
In 1976, two years after the discovery of adrafinil, its active metabolite modafinil was discovered. As of September 2011, Cephalon has discontinued Olmifon, its adrafinil product, while modafinil continues to be marketed.
Additive in United States dietary supplements
Adrafinil is sometimes included as an ingredient in misbranded or adulterated dietary supplements. One company had attempted to get a New Dietary Ingredient pre-market notification approved for adrafinil in 2017, but the Food and Drug Administration rejected it:
A position that adrafinil is an unapproved drug was indicated in a warning letter
Adrafinil containing products, purporting to be dietary supplements, are not allowed for use by military service members. This is because the Department of Defense considers adrafinil an unapproved drug.
New Zealand
In 2005 a Medical Classification Committee in New Zealand recommended to MEDSAFE NZ that adrafinil be classified as a prescription medicine due to risks of it being used as a party drug. At that time adrafinil was not scheduled in New Zealand.
Research
In a clinical trial with the tricyclic antidepressant clomipramine and placebo as comparators, adrafinil showed efficacy in the treatment of depression.