Mesocarb
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. It is currently under development for the treatment of Parkinson's disease and sleep disorders. It is taken by mouth.
The drug is a selective dopamine reuptake inhibitor. It is an unusual and unique DRI, acting as a negative allosteric modulator and non-competitive inhibitor of the dopamine transporter. 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 clinical trials for Parkinson's disease. The active enantiomer, armesocarb, is also being developed.
Medical uses
Mesocarb was originally developed in the Soviet Union in the 1970s for a variety of indications including asthenia, apathy, adynamia, and some clinical aspects of depression and schizophrenia. Mesocarb was used for counteracting the sedative effects of benzodiazepines, increasing workload capacity and cardiovascular function, treatment of attention deficit hyperactivity disorder in children, as a nootropic, and as a drug to enhance resistance to extremely cold temperatures. It has also been reported to have antidepressant and anticonvulsant properties.Available forms
Mesocarb was sold in Russia as 5mg oral tablets under the brand name Sydnocarb.Pharmacology
Pharmacodynamics
Mesocarb has been found to act as a selective dopamine reuptake inhibitor by blocking the actions of the dopamine transporter, and lacks the dopamine release characteristic of stimulants such as dextroamphetamine. It was the most selective DAT inhibitor amongst an array of other DAT inhibitors to which it was compared and, in 2017, was reported as the most selective DAT inhibitor described to date.The affinities of mesocarb at the human monoamine transporters in vitro have been reported to be 8.3nM for the dopamine transporter, 1,500nM for the norepinephrine transporter , and >10,000nM for the serotonin transporter . 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, and 494.9 ± 17.00μM at the SERT.
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.
Pharmacokinetics
s can be detected in urine for up to 10days after consumption.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.
Chemistry
Mesocarb, also known as 3--N-phenylcarbamoylsydnonimine, is a substituted phenethylamine and amphetamine and a mesoionic sydnone imine. It has the amphetamine backbone present, except that the RN has a complicated imine side chain present.Whereas mesocarb is a racemic mixture, the enantiopure levorotatory or -enantiomer is known as armesocarb. Armesocarb is described as the active enantiomer of mesocarb, whereas the - or D-enantiomer is said to be virtually inactive.
It is structurally related to feprosidnine.