Comparative study on barbiturates using isolated single neurons: GABA-mimetic action and augmentatory action on GABA response.

The comparisons among barbiturate derivatives in both GABA-mimetic action and augmentatory effect on GABA response were made. Experiments were performed on single neurones isolated from frog dorsal root ganglia, using a concentration clamp technique which combines a suction pipette technique (internal perfusion and voltage-clamp) with a rapid external solution exchange within 2 ms. Barbiturates employed here were secobarbital, pentobarbital, hexobarbital and phenobarbital. All barbiturates at the concentrations over 1 x 10(-4) M evoked the chloride current (ICl) dose-dependently. In the GABA-mimetic action of barbiturates the potency was in the order of secobarbital greater than pentobarbital greater than hexobarbital greater than phenobarbital. All barbiturates at the concentrations over 1 x 10(-6) M (but up to 1 x 10(-3) M) augmented the GABA-induced ICl. Potency order of barbiturates in augmenting GABA response was the same as that in their GABA-mimetic actions when the concentration was 1 x 10(-4) M or less. However at the concentration of 1 x 10(-3) M the efficacies of secobarbital and pentobarbital in augmenting GABA response were greatly reduced while the other two barbiturates produced further augmentation.