Modafinil

Modafinil
Clinical data
Trade names	Provigil, others
Other names	CRL-40476; CRC-40476; CEP-1538; DEP-1538; Diphenylmethyl-sulfinylacetamide
AHFS/Drugs.com	Monograph
MedlinePlus	a602016
License data	US DailyMed: Modafinil;
Pregnancy; category	AU: D; ;
Dependence; liability	Relatively low
Addiction; liability	Low
Routes of; administration	By mouth
Drug class	Stimulant;; Dopamine reuptake inhibitor;; Wakefulness-promoting agent;
ATC code	N06BA07 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); BR: Class B1 (Psychoactive drugs); CA: ℞-only; UK: POM (Prescription only); US: Schedule IV;
Pharmacokinetic data
Bioavailability	40–65% (based on urinary excretion)
Protein binding	~60% (mainly to albumin)
Metabolism	Liver (amide hydrolysis, S-oxidation, aromatic ring hydroxylation, glucuronide conjugation; CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5 involved)
Metabolites	Modafinil acid (35–65%); * Modafinil sulfone;
Onset of action	2–4 hours (peak)
Elimination half-life	Modafinil: 12–15 h; Armodafinil: 10–17 h; Esmodafinil: 3–5 h
Duration of action	11.5 h
Excretion	Urine: 80% (<=10% as modafinil, 35–51% as modafinil acid); Feces: 1.0%
Identifiers
	IUPAC name 2-(diphenylmethanesulfinyl)acetamide;
CAS Number	68693-11-8;
PubChem CID	4236;
IUPHAR/BPS	7555;
ChemSpider	4088;
UNII	R3UK8X3U3D;
KEGG	D01832;
ChEBI	CHEBI:31859;
ChEMBL	ChEMBL1373;
CompTox Dashboard (EPA)	DTXSID0023329 ;
ECHA InfoCard	100.168.719
Chemical and physical data
Formula	C15H15NO2S
Molar mass	273.35 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=S(C(c1ccccc1)c2ccccc2)CC(=O)N;
	InChI InChI=1S/C15H15NO2S/c16-14(17)11-19(18)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15H,11H2,(H2,16,17); Key:YFGHCGITMMYXAQ-UHFFFAOYSA-N;

Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat narcolepsy, sleep apnea, and shift work sleep disorder. It is taken by mouth. Modafinil is a first-line treatment for narcolepsy in the United States and Europe.

The mechanism of action is not fully understood, but modafinil acts mainly as an atypical dopamine reuptake inhibitor, increasing dopamine levels without the rapid signaling seen with classical stimulants such as amphetamine or cocaine. Unlike these drugs, modafinil has low addiction and dependence potential and does not produce strong euphoria, which contributes to its classification as a Schedule IV controlled substance in the United States. It is a prescription medication in most countries.

Modafinil is generally well-tolerated; common side effects include headache, nausea, anxiety, and insomnia. Rare but serious adverse effects include severe skin reactions such as Stevens-Johnson syndrome. Modafinil is contraindicated during pregnancy due to increased risk of birth defects.

Modafinil is used off-label as a cognitive enhancer or "smart drug" by students and professionals seeking improved focus. Research on cognitive effects in non-sleep-deprived individuals has yielded mixed results. Modafinil is banned in competitive sports by the World Anti-Doping Agency.

Developed in France in the 1970s by neurophysiologist Michel Jouvet, modafinil was approved for medical use in France in 1994 and in the United States in 1998. Generic versions became available in the US in 2012.