effect of different lipophyllic beta-blockers on the minimal electro-shock seizure threshold [MEST] in mice

ABSTRACT

The effect of different beta-blockers on the minimal electro-shock seizure threshold [MEST] in mice, an index of generalized seizure susceptibility, was studied. Equipolent doses of the lipophilic beta-adrenergic blockers propranolol, pindolol,.oxprenolol and metoprolol significantly reduced the MEST after acute or chronic use [P < 0.05], however, this reduction was not significantly dose-dependant or significantly different between them. These drugs also antagonised the effect of beta agonists sulbutamol and isoprenaline, as well as that of the antiepileptic drugs phenytoin, valproate and clonazepam in elevating the seizure threshold. No significant change in blood glucose level or brain GABA content accompanied these acute or chronic effects on MEST, except for propranolol. It is concluded that lipophylic beta-adrenergic blockers enhanced seizure susceptibility mainly by blocking beta-adrenoceptors in brain. The magnitude of. this effect does not seem to be significantly altered by the selectivity of the beta block or by the possession of partial agonist activity by some of these drugs