Esmodafinil

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
Identifiers
IUPAC name 2-[(S)-benzhydrylsulfinyl]acetamide
CAS Number	112111-47-4
PubChem CID	11173366
ChemSpider	9348458
UNII	152JRG3T0U
ChEBI	CHEBI:77591
ChEMBL	ChEMBL1672355
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
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 (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.

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.

Pharmacology

Pharmacodynamics

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

Pharmacokinetics

Esmodafinil possesses a substantially shorter elimination half-life (3–5 hours) compared to armodafinil (10–17 hours).

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.

A number of analogues of esmodafinil are known, including adrafinil, flmodafinil, fladrafinil, and others.

Preclinical research

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

Analysis in biological samples

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