Analysis of the Effect of Derivative of Pyridine Oximes (GIZh-298) on the Contentof Monoamines and Their Metabolites in the Structures of Rat BrainStructures during Seizures Caused by Maximum Electric Shock
We studied the effects of the potential antiepileptic compound GIZh-298 and the reference drug topiramate on the content of monoamines and their metabolites in the frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocampus of the rat brain after a generalized tonic-clonic seizure caused by maximum electric shock (MESH). We found that GIZh-298 (60 mg/kg i.p.) has a distinct anticonvulsant effect in the test of MESH antagonism, prevents an increase in the functional activity of the dopaminergic system in the striatum, as well as a decrease in the content of noradrenaline (NA) in the same structure. Topiramate (100 mg/kg i.p.), like GIZh-298, prevented the development of convulsive seizure caused by MESH, and increased the NA content to normal values in the striatum but did not affect the MESH-induced changes in the functional activity of the dopaminergic nigrostriatal system. Thus, it may be concluded that one of the mechanisms of anticonvulsant action of both GIZh-298 and topiramate in the test of MESH antagonism is the modulation of noradrenergic neurotransmission in the striatum; in addition, GIZh-298, in contrast to the topiramate, contributes to the weakening of the functional activity of the dopaminergic system, which is enhanced by MESH in this structure.