Esmodafinil
Unmarketed enantiomer of modafinil
From Wikipedia, the free encyclopedia
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]
-(+)-modafinil.svg)
(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] |
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| ECHA InfoCard | 100.234.492 |
| Chemical and physical data | |
| Formula | C15H15NO2S |
| Molar mass | 273.35 g·mol−1 |
| 3D model (JSmol) | |
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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 about 3-fold lower affinity for the dopamine transporter (DAT) compared to armodafinil or modafinil (Ki = 780 nM, 2,500 nM, and 2,300 nM, respectively).[5] It showed about 2-fold lower potency than armodafinil and about 1.5-fold higher potency than modafinil as a dopamine reuptake inhibitor (DRI) in vitro (IC50 = 8,700 nM, 4,000 nM, and 13,000 nM, respectively).[5] Both enantiomers of modafinil preferentially bind to the DAT in an inward facing conformation that is associated with atypical DRI profiles.[5][6] Esmodafinil was about 1.4- to 1.5-fold more potent than modafinil or armodafinil in substituting for cocaine in rodents.[5] Esmodafinil and armodafinil have been said to have approximately equipotent pharmacological effects but differing pharmacokinetics.[2]
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 elimination half-life of esmodafinil has been cited as reason to investigate armodafinil as a cocaine addiction treatment instead.[5]
Pharmacokinetics
Esmodafinil possesses a substantially shorter elimination half-life (3–5 hours) compared to armodafinil (10–17 hours) or modafinil (12–15 hours).[1][2][7][8][5][9]
Chemistry
Esmodafinil, or (S)-(+)-modafinil, is the enantiopure (S)-(+)-enantiomer of the racemic mixture modafinil, while armodafinil is the (R)-(–)-enantiomer.[1]
Analogues
A number of analogues of esmodafinil are known, including adrafinil, flmodafinil, fladrafinil, and others.[1]
Detection
Modafinil is considered a stimulant doping agent and as such is prohibited by World Anti-Doping Agency in sports competitions.[10] Modafinil enantiomers can be separately quantified in biological samples.[11]