Effects of calcium channel inhibitors upon the efficacy of common antiepileptic drugs

Eur J Pharmacol. 1990 Jan 25;176(1):75-83. doi: 10.1016/0014-2999(90)90134-r.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminophylline / pharmacology
  • Animals
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / pharmacology*
  • Body Temperature / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Drug Interactions
  • Electroshock
  • Female
  • Mice
  • Muscle Tonus / drug effects
  • Seizures / chemically induced
  • Seizures / prevention & control

Substances

  • Anticonvulsants
  • Calcium Channel Blockers
  • Aminophylline