Effect of phenoxybenzamine on the GABA system and on convulsive activity

The effect of phenoxybenzamine on the concentration of GABA and the aminooxyacetic acid (AOAA) induced accumulation of GABA in four brain regions was compared with its effect on the occurrence and latency of picrotoxin-induced convulsions. Also the effect of phenoxybenzamine on post-decapitation convulsions was followed. Whereas 0.1 mg/kg of phenoxybenzamine decreased the levels and the AOAA-induced accumulation of GABA in the substantia nigra and cerebellar cortex, 1.0 mg/kg produced an increased GABA accumulation in the substantia nigra. Both doses of the drug decreased the AOAA-induced accumulation of GABA in the cingulate cortex. Administration of phenoxybenzamine decreased the latency and increased or decreased the occurrence of picrotoxin-induced convulsions depending on the intensity of picrotoxin effect. Phenoxybenzamine also prolonged the latency and shortened the duration of post-decapitation convulsions in rats. The results suggest that two different mechanisms mediate the effects of phenoxybenzamine on the latency and occurrence of picrotoxin-induced convulsions.