A study of neuroprotective properties of the MGLUR4 receptor agonist – ZC64-0001 in comparison with Mexidol
Background: One of the most common neurodegenerative diseases is Parkinson's disease, which is based on the degeneration of dopaminergic neurons of the substantia nigra. The modern treatment for Parkinson's disease is a dopamine replacement therapy with levodopa, the use of which does not lead to a stop, progressive neurodegeneration and causes the appearance of side effects. Glutamate metabotropic receptors (mGluRs) are a promising application point for the search for new anti-Parkinsonian drugs. Group III metabotropic receptors are able to reduce the activity of NMDA receptors involved in the regulation of calcium levels in cells. Therefore, it is suggested that activation of these receptors may have a neuroprotective effect. The mGluR4 receptor agonist was synthesized at the «ChemRar». Further studies of the substance were carried out at the Scientific Research Institute "Pharmacology of Living Systems", BSU (Belgorod). The aim of the study:To study the neuroprotective efficacy of a pharmaceutical substance – ZC64-0001 in comparison with Mexidol in mice with cerebral ischemia. Materials and methods: The study was conducted on rats, divided into 9 groups of 10 animals. The test substance ZC64-0001 and the comparison drug Mexidol were administered intragastrically once a day for prophylactic and therapeutic purposes in various dosages. Then, the behavioral responses of animals were evaluated before the simulation of the IHM and on days 2, 7, and 14 after; level S100b and NSE after the cerebral ischemia. Results: In the course of the study it was found that the use of ZC64-0001 and Mexidol in the studied doses had a pronounced neuroprotective effect, manifested in a decrease in the severity of neurological deficit; and accelerating the disappearance of the symptoms of paralysis, ptosis, etc. At the same time, an improvement in motor activity indicators in the PLC and actimetry test was found, as well as a significant prevention of an increase in NSE and S100b protein. Conclusion: The neuroprotective effect of the mGluR4 receptor agonist is explained by their ability to reduce the activity of the NMDA receptor and, therefore, the risk of excitotoxicity.