Esmodafinil

Esmodafinil (also known as (S)-modafinil or (+)-modafinil; developmental code name CRL-40983) is the enantiopure (S)-(+)-enantiomer of modafinil. Unlike armodafinil ((R)-(–)-modafinil), esmodafinil has never been marketed on its own.^[3]

Esmodafinil

(S)-(+)-Modafinil
Clinical data
Other names	CRL-40983; (S)-Modafinil; S-Modafinil; (S)-(+)-Modafinil; (+)-Modafinil; NH-02D
Drug class	Atypical dopamine reuptake inhibitor; wakefulness-promoting agent
Pharmacokinetic data
Elimination half-life	3–5 hours[1][2]
Identifiers
IUPAC name 2-[(S)-benzhydrylsulfinyl]acetamide
CAS Number	112111-47-4
PubChem CID	11173366
ChemSpider	9348458
UNII	152JRG3T0U
ChEBI	CHEBI:77591
ChEMBL	ChEMBL1672355
CompTox Dashboard (EPA)	DTXSID70457709
ECHA InfoCard	100.234.492
Chemical and physical data
Formula	C15H15NO2S
Molar mass	273.35 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=CC=C(C=C1)C(C2=CC=CC=C2)[S@@](=O)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)/t19-/m0/s1 Key:YFGHCGITMMYXAQ-IBGZPJMESA-N

Esmodafinil is suspected to be less clinically useful for treating conditions that modafinil and armodafinil are marketed for, such as narcolepsy, shift work sleep disorder, and obstructive sleep apnea.^[4]

Pharmacology

Pharmacodynamics

Esmodafinil has a 3-fold lower affinity for the dopamine transporter (DAT) compared to armodafinil.^[5] Both enantiomers of modafinil preferentially bind to the DAT in an inward facing conformation that is associated with atypical dopamine reuptake inhibitor (DRI) profiles.^[5][6] Esmodafinil and armodafinil are said to have equipotent pharmacological effects but differing pharmacokinetics (see below).^[2]

Pharmacokinetics

Esmodafinil possesses a substantially shorter elimination half-life (3–5 hours) compared to armodafinil (10–17 hours).^{[1][2][7][8][5]}

Chemistry

See also: List of modafinil analogues and derivatives

Esmodafinil, or (S)-(+)-modafinil, is the enantiopure (S)-(+)-enantiomer of the racemic mixture modafinil, while armodafinil is the (R)-(–)-enantiomer.^[1]

A number of analogues of esmodafinil are known, including adrafinil, flmodafinil, fladrafinil, and others.^[1]

Preclinical research

Esmodafinil has been researched for the treatment of cocaine addiction.^[5][6] Like armodafinil, esmodafinil attenuates the effects of cocaine by occupying the dopamine transporter.^[6] While doing so, esmodafinil increases dopamine levels in the nucleus accumbens to a lesser extent than cocaine.^[5] However, the short half-life of esmodafinil has been cited as reason to investigate armodafinil as a cocaine addiction treatment instead.^[5]

Analysis in biological samples

Modafinil is considered a stimulant doping agent and as such is prohibited by World Anti-Doping Agency in sports competitions.^[9] Modafinil enantiomers can be separately quantified in biological samples.^[10]