Adrafinil

Adrafinil (CAS 63547-13-7; molecular formula C15H15NO3S; molecular weight 289.35) is the prodrug parent of modafinil, developed at Laboratoire Lafon in 1974 and marketed in France as Olmifon for narcolepsy and idiopathic hypersomnia in elderly patients. The compound is hydrolyzed in the liver to modafinil and modafinilic acid; modafinil is the active metabolite responsible for the wakefulness effect. The prodrug structure adds a hydroxylamide group to the modafinil scaffold, which is cleaved by hepatic amidases. The pharmacokinetic consequence is delayed onset (45 to 90 minutes versus 30 to 45 minutes for modafinil itself) and a less efficient conversion ratio (approximately 60 to 70 percent of an adrafinil dose appears as modafinil in plasma). The research literature reports correspondingly higher dose ranges than modafinil (approximately 600 to 1200 mg adrafinil yields serum modafinil concentrations comparable to 200 mg modafinil). Olmifon was discontinued in 2011 by the manufacturer (Cephalon), citing commercial reasons rather than safety, leaving research-grade adrafinil as the principal source for non-clinical use. The compound is not scheduled in the United States and is sold as a research chemical in most jurisdictions, though regulatory status varies. The principal safety concerns are hepatic enzyme elevation with chronic dosing (the hydrolysis to modafinil generates modafinilic acid as a co-product, which may stress hepatocyte detoxification pathways) and the same DRESS and SJS warnings as modafinil. Adrafinil should be avoided in subjects with pre-existing hepatic disease.