Adrafinil

Adrafinil

File:Adrafinil.svg
Clinical data
Synonyms	CRL-40028
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	N06BX17 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) Unscheduled (US)
Pharmacokinetic data
Bioavailability	80%
Metabolism	75% Hepatic, Cyp?
Elimination half-life	1 hour
Excretion	Renal
Identifiers
IUPAC name (RS)-2-benzhydrylsulfinylethanehydroxamic acid
CAS Number	63547-13-7 N
PubChem CID	3033226
ChemSpider	2297976 Y
UNII	BI81Z4542G
KEGG	D07348 Y
ChEMBL	ChEMBL93077 Y
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C15H15NO3S
Molar mass	289.351 g/mol
3D model (JSmol)	Interactive image
SMILES O=S(C(c1ccccc1)c2ccccc2)CC(=O)NO
InChI InChI=1S/C15H15NO3S/c17-14(16-18)11-20(19)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15,18H,11H2,(H,16,17) Y Key:CGNMLOKEMNBUAI-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Adrafinil (Olmifon) is a wakefulness-promoting agent (or eugeroic) used to relieve excessive sleepiness and inattention. It is also used off-label by individuals wishing to avoid fatigue, such as night workers or others who need to stay awake and alert for long periods of time.

Adrafinil is a prodrug; it is primarily metabolized in vivo to modafinil, resulting in nearly identical 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 does not currently have FDA approval and is thus unregulated in the United States. It was marketed in France and elsewhere in Europe under the trade name Olmifon until September 2011 when France's FDA-equivalent reassessed the drug and withdrew marketing permission, citing known adverse reactions and an unsatisfactory risk to benefit ratio.

History

Adrafinil was discovered in the late 1970s by scientists working with the French pharmaceutical company Group Lafon. First offered in France in 1986 as an experimental treatment for narcolepsy, Lafon later developed modafinil, the primary metabolite of adrafinil. Even though the exact mechanism of action is unclear, "most investigators assume that adrafinil and modafinil both serve as α₁-adrenergic receptor agonists." The evidence in support of this hypothesis is, however, weak and other mechanisms of action are probable. Modafinil possesses greater selective α₁-adrenergic activity than adrafinil, without many of adrafinil's common side effects (stomach pain, skin irritation, anxiety and (with prolonged use) elevated liver enzymes). This makes it important to monitor the liver of an individual using adrafinil for prolonged periods.

As of September 2011, Cephalon has discontinued Olmifon, its adrafinil product.

Legal status

Athletic doping

Adrafinil and its active metabolite modafinil were added to the list of substances prohibited for athletic competition according to World Anti-Doping Agency in 2004.

United States

In the United States, adrafinil is currently 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 not illegal to possess without a prescription and can be imported privately by citizens.

Canada

In Canada adrafinil is unregulated and can be legally purchased within the country as a research chemical, or imported privately by citizens.

New Zealand

In 2005 a Medical Classification Committee in New Zealand recommended to MEDSAFE NZ that adrafinil be classified as a prescription medicine.

"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."

See also

• Ampakine
• Armodafinil
• CRL-40941
• Fluorenol

External links

• "SID 184744 - PubChem Substance Summary". PubChem Project. National Center for Biotechnology Information. Retrieved 7 December 2005.
• "Adrafinil - Bank of Automated Data on Drugs". Bank of Automated Data on Drugs. VIDAL. Archived from the original on 5 October 2008. Retrieved 4 October 2008.
• Milgram, Norton W.; Callahan, Heather; Siwak, Christina (September 1992). "Adrafinil: A Novel Vigilance Promoting Agent" (PDF). CNS Drug Reviews. 5 (3): 193–212. doi:10.1111/j.1527-3458.1999.tb00100.x. open access publication – free to read
• Thobois, S. P.; Xie, J.; Mollion, H.; Benatru, I.; Broussolle, E. (August 2004). "Adrafinil-induced orofacial dyskinesia". Movement Disorders. 19 (8): 965–966. doi:10.1002/mds.20154. PMID 15300665.

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