Propranolol and metoprolol enhance the anticonvulsant action of valproate and diazepam against maximal electroshock.
The anticonvulsive potential of classical antiepileptics co-administered with beta-adrenergic receptor antagonists against generalized tonic-clonic seizures was evaluated in the model of maximal electroshock (MES)-induced convulsions. Propranolol, acebutolol, metoprolol and atenolol were tested in the doses not affecting the electroconvulsive threshold. Propranolol and metoprolol lowered the ED(50) of valproate and diazepam. Acebutolol reduced valproate's but not diazepam's ED(50) value. In contrast, hydrophilic atenolol, not penetrating via blood-brain barrier, affected neither the action of valproate nor diazepam. None of the studied drugs changed the protective activity of carbamazepine and phenytoin against MES. beta-blockers per se did not alter the motor performance of mice. Moreover, propranolol and metoprolol did not influence diazepam-evoked impairment of locomotor activity. The free plasma and brain levels of antiepileptic drugs were not affected by beta-blockers. In conclusion, the use of certain beta-adrenoceptor antagonists, such as propranolol and metoprolol, might improve the antiepileptic potential of valproate and diazepam.
Luchowska
Elzbieta
E
Department of Pharmacology and Toxicology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Luchowski
Piotr
P
Wielosz
Marian
M
Kleinrok
Zdzisław
Z
Czuczwar
Stanisław J
SJ
Urbańska
Ewa M
EM
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000378:metabolism / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011433:Propranolol / Q000627:therapeutic use*; D014635:Valproic Acid / Q000378:metabolism / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D000927:Anticonvulsants; D014635:Valproic Acid; D011433:Propranolol; D008790:Metoprolol; D003975:Diazepam