Effects of calcium channel inhibitors upon the efficacy of common antiepileptic drugs.
Diltiazem and nifedipine (both 1.25 mg/kg) markedly potentiated the protective action of carbamazepine and diphenylhydantoin against maximal electroshock-induced seizures in mice. These calcium channel inhibitors retained their activity at lower doses. Diltiazem and nifedipine (2.5 mg/kg) also moderately potentiated the efficacy of phenobarbital and valproate. Verapamil (up to 10 mg/kg) was not effective against the action carbamazepine, diphenylhydantoin, phenobarbital, and valproate. None of the calcium channel inhibitors used (up to 40 mg/kg) influenced aminophylline-induced convulsions and mortality. Moreover, the anti-aminophylline activity of valproate and phenobarbital was not potentiated by the calcium channel inhibitors in doses up to 10 mg/kg. Further, combination of carbamazepine, ethosuximide, and trimethadione with the calcium channel inhibitors (up to 10 mg/kg) did not offer any protection against aminophylline-induced convulsions. It can be concluded that calcium channel inhibitors enhance the protective efficacy of some antiepileptics against electroconvulsions. A pharmacokinetic interaction does not seem to be responsible for this effect.
Czuczwar
S J
SJ
Department of Pharmacology, Medical School, Lublin, Poland.
Chodkowska
A
A
Kleinrok
Z
Z
Małek
U
U
Jagiełło-Wójtowicz
E
E
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004347:Drug Interactions; D004597:Electroshock; D005260:Female; D051379:Mice; D009129:Muscle Tonus / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D000628:Aminophylline