ANTAGONISM OF γ‐AMINOBUTYRIC ACID AND GLYCINE BY CONVULSANTS IN THE CUNEATE NUCLEUS OF CAT

Abstract

1 Some convulsant substances have been applied to single neurones in the cat cuneate nucleus by microiontophoresis. Numerical values were derived for the effectiveness and selectivity of the substances as antagonists of γ-aminobutyric acid (GABA) and glycine. 2 (+)-Bicuculline methochloride was the most effective GABA antagonist and it also excited many neurones. It antagonized GABA in 93% of experiments but also antagonized glycine in 41% of experiments. In most experiments the antagonism of GABA was greater than the antagonism of glycine resulting in an overall selective antagonism of GABA that was statistically significant. Nevertheless, in only about one quarter of the individual experiments was the GABA antagonism substantial and the selectivity clearcut. 3 (+)-Bicuculline and picrotoxin were less easily applied to neurones by microiontophoresis and were found to antagonize GABA in 30% and 35% of experiments, respectively. They also antagonized glycine in 25% and 30% of experiments, respectively. Overall, neither substance could be shown to be selective, statistically, although in the few individual experiments where the GABA antagonism was substantial the antagonism was clearly selective. 4 (+)-Tubocurarine antagonized GABA in 59% and glycine in 32% of experiments and it also excited many neurones. Penicillin antagonized GABA in 33% of experiments without antagonizing glycine. Neither antagonist caused any substantial antagonisms of GABA and neither showed significant selectivity overall. (—)-Bicuculline methochloride, leptazol and bemegride antagonized GABA or glycine in less than 10% of experiments, although (—)-bicuculline methochloride excited most neurones. 5 Strychnine antagonized glycine in every experiment while antagonizing GABA in only 5% of experiments. In each individual experiment the antagonism of glycine was substantial and clearly selective, resulting in a statistically significant selectivity overall. 6 It is concluded that the selective glycine antagonist strychnine is considerably better than the presently available GABA antagonists for distinguishing between responses to GABA and glycine, when the antagonists are applied by microiontophoresis.