Stimulation of Gastric Mucosal Afferents with Adrenaline Potentiates the Anticonvulsive But Not the Sedative Action of Diazepam in Rats

Abstract

Intramuscular (i.m.) administration of diazepam (10 mg/kg) and adrenaline (0.2 mg/kg) prevented generalized clonic-tonic corasol seizures in 75‐80% of rats, but prevented local clonic corasol seizures in only 35‐40%. At this dose, diazepam induced powerful sedation, while adrenaline lacked this effect. Combined i.m. administration of diazepam at the threshold dose of 0.3 mg/kg with adrenaline at the threshold dose of 0.02 mg/kg prevented clonic-tonic corasol seizures in 85% of rats, though clonic seizures were prevented in only 35% of rats. Combined administration of diazepam (3 mg/kg) and adrenaline at the threshold dose of 0.02 mg/kg prevented not only clonic-tonic, but also clonic corasol seizures, in 95% and 80% of rats, respectively, without developing sedation. The basis of the mechanism of potentiation of the anticonvulsive action of diazepam is stimulation of gastric mucosal afferents by adrenaline.