The stimulatory effects of secobarbital and pregnanolone on the GABAA receptor can be blocked selectively.

The stimulatory effects of secobarbital and pregnanolone on GABA receptor binding could be distinguished by their sensitivity to blockade by phenobarbital, avermectin B1a and picrotoxinin. Phenobarbital (1 mM) and avermectin (10(-9)-10(-6) M) inhibited the stimulation of [3H]muscimol binding to pig brain membranes caused by secobarbital but not that caused by pregnanolone. In contrast, enhancement of [3H]muscimol binding by pregnanolone showed a greater sensitivity to the inhibitory effects of picrotoxinin. These results, together with data demonstrating an additivity of barbiturate- and steroid-induced effects, indicate that these two classes of modulators may interact with the GABAA receptor through different sites.