study on the effect of propranolol on seizure threshold in mice: its possible mechanisms and interaction

ABSTRACT

The effect of propranolol on the minimal electroshock seizure threshold [MEST] in mice, an index of generalised seizure susceptibility, was studied This lipophylic, non-selective beta-adrenergic blocker reduced the MEST after acute or chronic use [P < 0.01]; it also antagonised the effect of the beta-adrenergic agonists isoprenaline and salbutamol as well as that of the anti-epileptic agents phenytoin, valproate, and clonazepam in elevating the MEST. These acute or chronic effects were not accompanied by any significant hypoglycaemia, but the chronic effect was associated with a significant reduction in brain GABA content [P <0.01]. Hepatic microsomal enzyme induction with rifamycin effectively blocked the chronic effect of the drug in reducing the MEST. It is concluded that the effect of propranolol in enhancing seizure susceptibility is due the parent compound and is mainly mediated by blocking central beta-adreno ceptors; reduction in brain GABA might be implicated in the chronic effect of this drug. It is possible that this drug could aggravate or disturb the control of generalized epilepsy in man