Adrafinil
/ Pro-drug of modafinil (small molecule, hydroxyamide of modafinil)ALIAS · Olmifon (trade — formerly EU)
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Tier 2. Was approved in France and several EU countries as Olmifon for narcolepsy and age-related vigilance disorders from the 1980s. Voluntarily withdrawn by Cephalon in 2011 — a business decision linked to focus on its active metabolite modafinil rather than a safety-driven action. Not approved in the US. Sold in the US through nootropic vendor channels; no longer available through any approved pharmaceutical channel in any major market.
Adrafinil is a hydroxyamide pro-drug that is hepatically metabolised to modafinil (and to the inactive modafinil-acid metabolite). The wakefulness-promoting pharmacology is therefore inherited from modafinil, which has weak dopamine-reuptake inhibition and effects on histamine, orexin, and noradrenaline systems. Because conversion is incomplete and slower than direct modafinil dosing, adrafinil produces a delayed onset and lower modafinil exposure per milligram than modafinil itself. The hepatic conversion is the basis for adrafinil's higher liver-enzyme-elevation profile relative to modafinil.
Tier 2. The published human-evidence base centres on aged-population vigilance and cognitive studies in Europe (1980s–1990s, principally French-language literature) and on the canine cognitive-aging model (Milgram, Siwak, and colleagues). The canine work is methodologically rigorous within its species and provides the most cited preclinical pharmacology, but does not substitute for contemporary human RCT data; the French elderly-vigilance literature is mostly outside indexed English-language journals.
Class concerns are dominated by hepatic enzyme elevation — the asymmetric carbon and the amide hydrolysis chemistry mean adrafinil produces measurable transaminase elevation more frequently than modafinil at equivalent wakefulness exposure. Stevens-Johnson syndrome and DRESS reactions documented for modafinil are read-across concerns. No comprehensive contemporary human safety database is available because Olmifon was withdrawn before modern post-marketing pharmacovigilance applied to nootropic use.
Regulatory status
- FDA status:
- Not FDA-approved
Olmifon withdrawal was a Cephalon business decision favouring modafinil rather than a safety action — but the practical effect is that adrafinil is no longer available through any approved pharmaceutical channel anywhere. Vendor-sold adrafinil in the US is not pharmaceutical-grade material and is purchased through nootropic-supplement channels that do not have the identity, purity, or hepatic-monitoring infrastructure of the original Olmifon prescription pathway. Subjects choosing modafinil directly avoid the hepatic-conversion step entirely.