Adrafinil

Overview

Adrafinil is a non-peptide synthetic eugeroic (wakefulness-promoting agent) and diphenylmethylsulfinyl-acetohydroxamic acid derivative that functions as a prodrug of modafinil. It was approved in France (marketed as Olmifon) from 1984 to 2011 for narcolepsy but was voluntarily withdrawn due to hepatotoxicity concerns and an unfavorable risk-benefit ratio. Adrafinil is not currently approved in any jurisdiction; the FDA classifies it as an unapproved new drug when sold as a dietary supplement. It is prohibited in competitive sport under WADA’s S6.a Non-Specified Stimulants category.

Mechanism of Action

Adrafinil is considered pharmacologically inactive or only weakly active and functions as a prodrug: it is hydrolyzed in the liver to its active metabolite modafinil (plus inactive modafinil acid), which produces the wake-promoting effect. Modafinil’s mechanism is not fully settled; in vivo rat data found modafinil acts as a weak, atypical dopamine transporter (DAT) inhibitor (IC50 ~4.0 µM for [³H]DA uptake), increasing locomotor activity and extracellular dopamine without affecting serotonin. This is modafinil pharmacology in rats, not a direct adrafinil human study, presented as the best-sourced mechanistic account available.

Research Summary

Adrafinil was approved in France for narcolepsy (1985) after initial human testing in 1977–1978, but was voluntarily withdrawn in September 2011 due to hepatotoxicity concerns and an unfavorable risk-benefit ratio. No current registered interventional clinical trials exist; the only registered study is an observational survey listing adrafinil as a queried substance. One published forensic study (n=1) detected adrafinil (0.8 ng/mg) and modafinil (0.5 ng/mg) in beard hair 10 days after a single 200 mg oral dose in one adult volunteer. Preclinical studies in aged beagle dogs found oral 20 mg/kg adrafinil improved discrimination learning but impaired working memory in a delayed nonmatching-to-position task over 8 days. Rat studies of the metabolite modafinil showed dose-dependent increases in locomotor activity and extracellular dopamine.

Reported Side Effects

• Hepatotoxicity/elevated liver enzymes with prolonged use
• Unapproved drug status in the US (FDA enforcement action)
• Prohibited in competitive sport (WADA S6.a)
• Working-memory impairment (aged beagle dog study, 20 mg/kg)
• No validated human safety profile from controlled trials

Compare Adrafinil with Others

Research References

• Adrafinil, Compound Summary for CID 3033226.
• ADRAFINIL substance record (BI81Z4542G).
• adrafinil drug card.
• Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil. 2009. PMID 19197004.

Frequently asked questions

Has Adrafinil been independently lab-tested?

Disclosed Labs has collected 3 Certificates of Analysis (COA) for Adrafinil from 2 independent testing labs. 1 vendor has submitted material for testing. Products average 99.8% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/adrafinil/testing.

What is the average purity of Adrafinil on the market?

Based on 3 COAs analyzed by Disclosed Labs, Adrafinil products average 99.8% (±0.0%) tested purity. Individual vendor results vary; see per-vendor COA data at https://www.disclosedlabs.com/peptides/adrafinil/coas.

How does Adrafinil work?

Adrafinil is considered pharmacologically inactive or only weakly active and functions as a prodrug: it is hydrolyzed in the liver to its active metabolite modafinil (plus inactive modafinil acid), which produces the wake-promoting effect. Modafinil’s mechanism is not fully settled; in vivo rat data found modafinil acts as a weak, atypical dopamine transporter (DAT) inhibitor (IC50 ~4.0 µM for [³H]DA uptake), increasing locomotor activity and extracellular dopamine without affecting serotonin. This is modafinil pharmacology in rats, not a direct adrafinil human study, presented as the best-sourced mechanistic account available.

What does the research say about Adrafinil?

Adrafinil was approved in France for narcolepsy (1985) after initial human testing in 1977–1978, but was voluntarily withdrawn in September 2011 due to hepatotoxicity concerns and an unfavorable risk-benefit ratio. No current registered interventional clinical trials exist; the only registered study is an observational survey listing adrafinil as a queried substance. One published forensic study (n=1) detected adrafinil (0.8 ng/mg) and modafinil (0.5 ng/mg) in beard hair 10 days after a single 200 mg oral dose in one adult volunteer. Preclinical studies in aged beagle dogs found oral 20 mg/kg adrafinil improved discrimination learning but impaired working memory in a delayed nonmatching-to-position task over 8 days. Rat studies of the metabolite modafinil showed dose-dependent increases in locomotor activity and extracellular dopamine.