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.

Synergistic anticonvulsant action of diazepam & clonazepam with amino-oxyacetic acid against isoniazid-induced convulsions in rats.

The protective effect of two benzodiazepine compounds, diazepam and clonazepam was tested against isoniazid (INH)- induced convulsions in rats pretreated with the gamma-amino-butyric acid (GABA) transaminase inhibitor viz., aminooxyacetic acid (AOAA), and the result was compared with that produced by the two drugs independently. Rats treated 6 h and not 30 min previously with AOAA showed a dose-dependent inhibition of INH-induced convulsions. In these animals both diazepam and clonazepam showed a greater protective effect than that produced by them alone. It is suggested from these findings that, even if their anticonvulsant mechanisms are distinct, with or without the involvement of GABA, AOAA and the benzodiazepine compounds seem to act synergistically against INH-induced convulsions.