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Mesocarb, sold under the brand name Sidnocarb or Sydnocarb and known by the developmental code name MLR-1017, is a psychostimulant medication which has been used in the treatment of psychiatric disorders and for a number of other indications in the Soviet Union and Russia.Schweizerischer Apotheker-Verein (2025). 9783887630751, Medpharm Scientific Publishers. . ISBN 9783887630751 It is currently under development for the treatment of Parkinson's disease and . It is taken by mouth.
The drug is a selective dopamine reuptake inhibitor (DRI). It is an unusual and unique DRI, acting as a negative allosteric modulator and non-competitive inhibitor of the dopamine transporter (DAT). Chemically, mesocarb contains amphetamine within its structure but has been modified and extended at the amine with a sydnone imine-containing moiety.
Mesocarb was first described by 1971. It was used as a pharmaceutical drug until 2008. In 2021, its nature as a DAT allosteric modulator was reported. As of February 2023, mesocarb was in phase 1 for Parkinson's disease. The active enantiomer, armesocarb, is also being developed.
The affinities (Ki) of mesocarb at the human monoamine transporters in vitro have been reported to be 8.3nM for the dopamine transporter (DAT), 1,500nM for the norepinephrine transporter (NET) (181-fold lower than for the DAT), and >10,000nM for the serotonin transporter (SERT) (>1,205-fold lower than for the DAT). The inhibitory potencies () of mesocarb at the human monoamine transporters in vitro have been reported to be 0.49 ± 0.14μM at the DAT, 34.9 ± 14.08μM at the NET (71-fold lower than for the DAT), and 494.9 ± 17.00μM at the SERT (1,010-fold lower than for the DAT).
In 2021, it was discovered that mesocarb is not a conventional DRI but acts as a DAT allosteric modulator or non-competitive inhibitor. In accordance with its nature as an atypical DAT blocker, the drug has atypical effects relative to conventional DRIs. As an example, it shows greater antiparkinsonian activity relative to other DRIs in animals.
Similarly to other DRIs, mesocarb has been found to possess wakefulness-promoting effects.
Mesocarb had erroneously been referred to as a prodrug of amphetamine. However, this was based on older literature that relied on gas chromatography as an analytical method. Subsequently, with the advent of mass spectroscopy, it has been shown that presence of amphetamine in prior studies was an artifact of the gas chromatography method. More recent studies using mass spectroscopy show that negligible levels of amphetamine are released from mesocarb metabolism.
Whereas mesocarb (MLR-1017) is a racemic mixture, the enantiopure drug levorotatory or ( R)-enantiomer is known as armesocarb (MLR-1019). Armesocarb is described as the active enantiomer of mesocarb, whereas the ( S)- or D-enantiomer is said to be virtually inactive.
It is structurally related to feprosidnine (Sydnophen; 3-(α-methylphenylethyl)sydnone imine). (2025). 9783642003356, Springer Berlin Heidelberg. ISBN 9783642003356
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