Dihydroergotoxine and the Seizure Threshold1

Abstract

Dihydroergotoxine administration shortened the latency of allylglycine-and picrotoxin-induced convulsions in rats and increased the incidence of convulsions elicited by picrotoxin, i.e., it lowered ED(50) for picrotoxin. The same drug (0.1-10.0 mg/kg) decreased the levels of γ-aminobutyric acid (GABA) in the caudate nucleus and cingulate cortex, but enhanced the aminooxyacetic acid induced accumulation of GABA indicating an increased synthesis of GABA in these brain regions. The concentrations of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, noradrenaline, and dopamine in the whole rate brain were not affected with doses of dihydroergotoxine up to 10.0 mg/kg, but this dose of the drug slowed down the turnover of dopamine, as evidenced by a diminished disappearance of dopamine induced by α-methyl-p-tyrosine administration. The results suggest that dihydroergotoxine decreases GABA-ergic transmission and, therefore, presumably lowers the seizure threshold.