Chemistry:Armesocarb
Armesocarb (developmental code name MLR-1019), also known as (R)-mesocarb or L-mesocarb, is a selective atypical dopamine reuptake inhibitor (DRI). It is currently under development for the treatment of Parkinson's disease and sleep disorders.[1][2]
It is the active (R)-enantiomer of the formerly clinically used stimulant-like drug mesocarb (MLR-1017; brand name Sydnocarb).[1][2][3]
Pharmacology
Mesocarb is known to be a highly selective DRI.[2] However, in 2021, it was discovered that mesocarb is not a conventional DRI but acts as a dopamine transporter (DAT) allosteric modulator or non-competitive inhibitor.[4][5][6]
In accordance with its nature as an atypical DAT blocker, the drug exhibits atypical effects compared to conventional DRIs.[4][5][6][2] For example, mesocarb shows greater antiparkinsonian activity in animals compared to other DRIs.[2]
Mesocarb has wakefulness-promoting effects in animals.[2][7] Armesocarb, as the active enantiomer of mesocarb, shows greater therapeutic potency than the racemic form in animals.[1][2][3] In contrast, the (S)- or D-enantiomer of mesocarb is virtually inactive in animal behavioral tests.[3]
History
Armesocarb was first described in the scientific literature as an enantiopure compound by 2005 and again in 2017.[3][2]
Clinical studies
As of April 2023, armesocarb is undergoing phase 1 clinical trials for Parkinson's disease and is in preclinical development for sleep disorders.[1] The latter indication may specifically target excessive daytime sleepiness (EDS) in people with Parkinson's disease.[2] Armesocarb is also in development for the treatment of levodopa-induced dyskinesia.[8][2]
See also
- MRZ-9547 ((R)-phenylpiracetam)
- List of Russian drugs
References
- ↑ 1.0 1.1 1.2 1.3 "Melior Pharmaceuticals". 28 April 2023. https://adisinsight.springer.com/drugs/800034792.
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 "Phenotypic Screening". Drug Repositioning. Frontiers in Neurotherapeutics. Boca Raton: CRC Press. 14 July 2017. pp. 121–145. doi:10.4324/9781315373669-7. ISBN 978-1-315-37366-9. https://www.researchgate.net/publication/333583200.
- ↑ 3.0 3.1 3.2 3.3 "Comparative Molecular Model Estimation of the Affinity of Phenylethylamines to the Binding Sites of Membrane Transporters". Pharmaceutical Chemistry Journal 39 (4): 169–175. 2005. doi:10.1007/s11094-005-0110-3. ISSN 0091-150X.
- ↑ 4.0 4.1 "Overview of the structure and function of the dopamine transporter and its protein interactions". Frontiers in Physiology 14. 2023. doi:10.3389/fphys.2023.1150355. PMID 36935752.
- ↑ 5.0 5.1 "Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments". Current Research in Physiology 7. 2024. doi:10.1016/j.crphys.2024.100125. PMID 38836245.
- ↑ 6.0 6.1 "Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter". Biomedicines 9 (6): 634. June 2021. doi:10.3390/biomedicines9060634. PMID 34199621.
- ↑ "Characterization of pharmacological and wake-promoting properties of the dopaminergic stimulant sydnocarb in rats". The Journal of Pharmacology and Experimental Therapeutics 337 (2): 380–390. May 2011. doi:10.1124/jpet.111.178947. PMID 21300706.
- ↑ "Emerging drugs for the treatment of L-DOPA-induced dyskinesia: an update". Expert Opinion on Emerging Drugs 25 (2): 131–144. June 2020. doi:10.1080/14728214.2020.1763954. PMID 32366130.
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