Influence of β- blockers on the activity of some anti-epileptic drugs on convulsions induced by picrotoxin in mice

Abstract

Adrenergic β-receptor blockers are widely used in clinic for the management of cardiovascular disease and some other illnesses. However, this group of drugs known to cause central nervous system side effects such as drowsiness, sleep disturbance, hallucination, migraine and tremors. As anti-epileptic drugs exert their action mainly through the inhibition of the central nervous system to decrease the firing and the excitability of neurons. Accordingly, β-blockers might influence the pharmacological activity of anti-epileptic drugs. Aim:The aims of this study is to investigate the influence of β –blockerson the anti-convulsant activity of two anti-epileptic drugs, i.e. phenytoin and phenobarbital. Methods: Three beta blockers with different β-receptor blocking selectivity and degree of solubility (atenolol, metoprolol, and propranolol) were injected intraperitoneally (IP) into mice either alone or in combination with phenytoin or phenobarbital. After 30 min mice were injected with picrotoxin (8mg/kg) to induce convulsions. Convulsion parameters recorded were; the onset of jerks, number of tonic and clonic convulsions, and % mortality. Results: Picrotoxin produced 100% death in all control animals. However, mosttheanimals treated with antiepileptics alone or in combination with β-blockers were protected from death. The effect of phenytoin on the onset of convulsions was significantlyenhanced when it combined with β-blockers. However, in regard to phenobarbital only the increase was noticed with propranolol. Giving phenytoin with β-blockers improves its effect in reducing clonic convulsion, whereas, no change in phenobarbital activity when administered together with β-blockers. Combination of either phenytoin or phenobarbital with β-blockers did not result in any significant change in their ability to reduce tonic convulsions except when phenytoin co-administered with metoprolol a significant decrease was observed. Conclusion: The administration of β-blockers in concomitant with phenytoin and phenobarbital increased their anticonvulsant activity. However, β-blockers alone could have some protective effect against convulsions.