Chemistry: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.[1]
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.[2]
Pharmacology
Pharmacodynamics
Esmodafinil has a 3-fold lower affinity for the dopamine transporter (DAT) compared to armodafinil.[3] Both enantiomers of modafinil preferentially bind to the DAT in an inward facing conformation that is associated with atypical dopamine reuptake inhibitor (DRI) profiles.[3][4] Esmodafinil and armodafinil are said to have equipotent pharmacological effects but differing pharmacokinetics (see below).[5]
Pharmacokinetics
Esmodafinil possesses a substantially shorter elimination half-life (3–5 hours) compared to armodafinil (10–17 hours).[6][5][7][8][3]
Chemistry
Esmodafinil, or (S)-(+)-modafinil, is the enantiopure (S)-(+)-enantiomer of the racemic mixture modafinil, while armodafinil is the (R)-(–)-enantiomer.[6]
A number of analogues of esmodafinil are known, including adrafinil, flmodafinil, fladrafinil, and others.[6]
Preclinical research
Esmodafinil has been researched for the treatment of cocaine addiction.[3][4] Like armodafinil, esmodafinil attenuates the effects of cocaine by occupying the dopamine transporter.[4] While doing so, esmodafinil increases dopamine levels in the nucleus accumbens to a lesser extent than cocaine.[3] However, the short half-life of esmodafinil has been cited as reason to investigate armodafinil as a cocaine addiction treatment instead.[3]
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]
References
- ↑ "NCATS Inxight Drugs — MODAFINIL, (S)-" (in en). https://drugs.ncats.io/drug/152JRG3T0U.
- ↑ "Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial". Neurology Research International 2011. 2011-06-01. doi:10.1155/2011/514351. PMID 21766023.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 "R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse". Biological Psychiatry 72 (5): 405–413. September 2012. doi:10.1016/j.biopsych.2012.03.022. PMID 22537794.
- ↑ 4.0 4.1 4.2 "The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors". PLOS ONE 6 (10). 2011. doi:10.1371/journal.pone.0025790. PMID 22043293. Bibcode: 2011PLoSO...625790S.
- ↑ 5.0 5.1 Cite error: Invalid
<ref>tag; no text was provided for refs namedHerseyTanda2024 - ↑ 6.0 6.1 6.2 "Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects". Substance Abuse 41 (2): 155–173. 2020. doi:10.1080/08897077.2019.1700584. PMID 31951804.
- ↑ "Pharmacokinetic evaluation of armodafinil for the treatment of bipolar depression". Expert Opinion on Drug Metabolism & Toxicology 8 (9): 1189–1197. September 2012. doi:10.1517/17425255.2012.708338. PMID 22803602.
- ↑ "Armodafinil". CNS Drugs 23 (9): 793–803. September 2009. doi:10.2165/11203290-000000000-00000. PMID 19689169.
- ↑ "The Prohibited List". https://www.wada-ama.org/en/prohibited-list.
- ↑ "New enantioselective LC method development and validation for the assay of modafinil". Journal of Pharmaceutical and Biomedical Analysis 138: 267–271. May 2017. doi:10.1016/j.jpba.2017.02.028. PMID 28231529.
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