The synergistic protective effect of propranolol & aminooxyacetic acid against picrotoxin-induced myoclonus in rats.

The effect of propranolol was assessed against myoclonus induced by picrotoxin (a known GABA antagonist) in a dose of 3 mg/kg and allylglycine (the inhibitor of GABA synthesis and release) in a dose of 150 mg/kg. A dose-dependent (0.5-2 mg/kg) protective effect was found against both models. Pretreatment of rats with a GABA-reducing dose (100 mg/kg, nonmyoclonic) of allylglycine produced no change in the effect of propranolol against picrotoxin-induced myoclonus. Propranolol thus inhibited myoclonic responses when both the receptor activity and the functional pool of GABA were impaired, suggesting that it produces as antimyoclonic action without the involvement of GABA. However, the drug seems to show a synergistic action with GABA-ergic agents, as greater protection was observed in rats treated concurrently with propranolol and amino-oxyacetic acid, an inhibitor of GABA degradation.