Stimulation of Gastric Mucosal Afferents with Mesaton Potentiates the Anticonvulsant and Eliminates the Sedative Actions of Sodium Valproate in Rats with Corasol Kindling

Abstract

Chronic oral sodium valproate given at high doses (100–200 mg/kg) suppressed the development of generalized clonic-tonic corasol (pentylenetetrazole) kindled convulsions in 100% of rats but prevented local clonic kindled convulsions in only 33–57%. At these doses, sodium valproate induced strong sedation. Combined chronic oral administration of Mesaton at the threshold dose of 0.2 mg/kg, inactive when give alone, and sodium valproate at the high doses of 100 and 200 mg/kg potentiated the anticonvulsant action of sodium valproate and prevented not only clonic-tonic kindled convulsions in 100% of rats, but also clonic kindled convulsions in 86–100% of rats, and also increased the anticonvulsant activity of valproate by factors of 1.7–1.9. These combinations of sodium valproate with Mesaton did not induce any sedative side effect. The mechanism of potentiation of the anticonvulsant effect and elimination of the sedative side effect of high-dose sodium valproate is based on stimulation of gastric mucosal afferents by Mesaton.