Armesocarb Explained

Class:

Atypical dopamine reuptake inhibitor

Cas Number:

34262-84-5

Pubchem:

7130196

Chemspiderid:

5473777

Unii:

UMT8MP2NDU

Synonyms:

(R)-Mesocarb; L-Mesocarb; MLR-1019; MLR1019

Iupac Name:

N-phenyl-N-[3-[(2''R'')-1-phenylpropan-2-yl]oxadiazol-3-ium-5-yl]carbamimidate| C=18 | H=18 | N=4 | O=2| SMILES = C[C@H](CC1=CC=CC=C1)[N+]2=NOC(=C2)N=C(NC3=CC=CC=C3)[O-]| StdInChI = 1S/C18H18N4O2/c1-14(12-15-8-4-2-5-9-15)22-13-17(24-21-22)20-18(23)19-16-10-6-3-7-11-16/h2-11,13-14H,12H2,1H3,(H-,19,20,21,23)/t14-/m1/s1| StdInChIKey = OWFUPROYPKGHMH-CQSZACIVSA-N}}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).

Pharmacology

Mesocarb is known to be a highly selective DRI. 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.^{[3] [4] [5]}

In accordance with its nature as an atypical DAT blocker, the drug exhibits atypical effects compared to conventional DRIs. For example, mesocarb shows greater antiparkinsonian activity in animals compared to other DRIs.

Mesocarb has wakefulness-promoting effects in animals.^[6] Armesocarb, as the active enantiomer of mesocarb, shows greater therapeutic potency than the racemic form in animals. In contrast, the (S)- or D-enantiomer of mesocarb is virtually inactive in animal behavioral tests.

History

Armesocarb was first described in the scientific literature as an enantiopure compound by 2005 and again in 2017.^[7]

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. The latter indication may specifically target excessive daytime sleepiness (EDS) in people with Parkinson's disease. Armesocarb is also in development for the treatment of levodopa-induced dyskinesia.^[8]

See also

• MRZ-9547 ((R)-phenylpiracetam)
• List of Russian drugs

References

Notes and References

1. Web site: Melior Pharmaceuticals . AdisInsight . 28 April 2023 . 26 September 2024.
2. Book: Macolino-Kane CM, Ciallella JR, Lipinski CA, Reaume AG . Drug Repositioning . Phenotypic Screening . CRC Press . Boca Raton . Frontiers in Neurotherapeutics . 14 July 2017 . 978-1-315-37366-9 . 10.4324/9781315373669-7 . 121–145 .
3. Nepal B, Das S, Reith ME, Kortagere S . Overview of the structure and function of the dopamine transporter and its protein interactions . Frontiers in Physiology . 14 . 1150355 . 2023 . 36935752 . 10020207 . 10.3389/fphys.2023.1150355 . free .
4. Nguyen H, Cheng MH, Lee JY, Aggarwal S, Mortensen OV, Bahar I . Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments . Current Research in Physiology . 7 . 100125 . 2024 . 38836245 . 11148570 . 10.1016/j.crphys.2024.100125 .
5. Aggarwal S, Cheng MH, Salvino JM, Bahar I, Mortensen OV . Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter . Biomedicines . 9 . 6 . 634 . June 2021 . 34199621 . 8227285 . 10.3390/biomedicines9060634 . free .
6. Gruner JA, Mathiasen JR, Flood DG, Gasior M . 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 . 21300706 . 10.1124/jpet.111.178947 .
7. Al'tshuler RA . Comparative Molecular Model Estimation of the Affinity of Phenylethylamines to the Binding Sites of Membrane Transporters . Pharmaceutical Chemistry Journal . 39 . 4 . 2005 . 0091-150X . 10.1007/s11094-005-0110-3 . 169–175.
8. AlShimemeri S, Fox SH, Visanji NP . Emerging drugs for the treatment of L-DOPA-induced dyskinesia: an update . Expert Opinion on Emerging Drugs . 25 . 2 . 131–144 . June 2020 . 32366130 . 10.1080/14728214.2020.1763954 .