Participation of Brain Receptors in the Mechanism of Anticonvulsant Action of the New 4-Benzoylpyridine Oxime Derivative GIZH-298.

Abstract—The aim of this work was to study the involvement of the glutamate, dopamine, and serotonin receptors in the mechanism of the anticonvulsant action of the 4-benzoylpyridine oxime derivative (GIZH-298). After a single corneal exposure to the maximum electric shock (MES) and subsequent tonic–clonic seizures, an increase in the density (Bmax) of NMDA receptors in the hippocampus by 27% and a decrease in the number of mGluII receptors (mGluR2/ 3) by 25% in the prefrontal cortex of the brain of rats were noted. At the same time, the number of 5-HT2A receptors in the prefrontal cortex did not change. GIZH-298 (60 mg/kg) with a single application inhibits convulsive reactions but does not affect the quantitative changes induced by MES in glutamate receptors and does not affect them under normal conditions without MES. In tests on mice, subchronic (5 days) corneal exposure to MES reduced the density (Bmax) of D₂ receptors in the striatum by 17% and did not change this parameter in the prefrontal cortex. GIZH-298 (60 mg/kg/5 days) eliminates clonic–tonic convulsions in mice and prevents a decrease in the number of D₂ receptors from striatal membranes and also increases their number by 13% in mice without MES in the same structure. The data we obtained indicate significant changes in the functional activity of the NMDA, mGluII, and D₂ receptors in the brains of animals that suffered seizures. The anticonvulsant effects of GIZH-298 are accompanied by the restoration of the number of D₂ receptors in the striatum. [ABSTRACT FROM AUTHOR]