Esmodafinil (also known as (S)-modafinil or (+)-modafinil; developmental code name CRL-40983) is the enantiopure drug ( 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 pharmacology effects but differing
pharmacokinetics (see below).
Pharmacokinetics
Esmodafinil possesses a substantially shorter elimination half-life (3–5hours) compared to
armodafinil (10–17hours).
Chemistry
Esmodafinil, or (
S)-(+)-modafinil, is the
enantiopure drug (
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.
