Antagonism of seizures induced by the administration of the endogenous convulsant quinolinic acid into rat brain ventricles.

Abstract

The effect of pretreatment with drugs on generalized clonic-tonic seizures induced by intracerebroventricular (i.c.v.) administration of the endogenous convulsant quinolinic acid (QUIN, 50 micrograms) was studies in rats. Of the inhibitory amino acids tested, only 1-glycine (50 and 100 micrograms, i.c.v.) diminished the number of animals with seizures while taurine and GABA were ineffective. Of the kynurenine metabolites, only kynurenic acid (50 micrograms, i.c.v.) prevented seizures and lethality. Picolinic acid, nicotinic acid and nicotinamide were ineffective. The standard anticonvulsants phenobarbital, diphenylhydantoin and primidone were effective antagonists of QUIN-induced seizures at doses which did not influence pentylenetetrazol seizures. However, the only drug which completely prevented QUIN-induced seizures was diazepam (10 mg/kg). It also prevented pentylenetetrazol seizures in rats in a four times lower dose. The GABA derivatives sodium hydroxybutyrate and phenibut (beta-phenyl-GABA), which are effective QUIN-antagonists in mice, were found to be ineffective in rats. Species differences between rats and mice in the efficacy of antagonists QUIN are discussed.