Influence of calcium channel inhibitors upon the anticonvulsant efficacy of common antiepileptics against pentylenetetrazol-induced convulsions in mice.
Among three calcium channel inhibitors studied, nifedipine (20 mg/kg) moderately inhibited pentylenetetrazol (115 mg/kg, s.c.)-induced convulsions, whilst diltiazem (up to 20 mg/kg) and verapamil (up to 20 mg/kg) were without effect. The combinations of nifedipine (10 and 20 mg/kg) with valproate (100 mg/kg) or phenobarbital (6.25 mg/kg) resulted in significant protection against pentylenetetrazol-induced seizures. Combined treatment of nifedipine (5-20 mg/kg) with ethosuximide (100 mg/kg) also provided a clearcut anticonvulsant action. The antiepileptic drugs alone, in the above doses, were ineffective. The combination of diltiazem (10-20 mg/kg) and ethosuximide (100 mg/kg) produced protection against pentylenetetrazol, comparable to that of ethosuximide (200 mg/kg) alone. No pharmacokinetic interactions were found in the case of ethosuximide, whilst nifedipine (10 mg/kg) increased the levels of phenobarbital and valproate in plasma. The combination of diltiazem with the remaining antiepileptics were ineffective. Verapamil (up to 20 mg/kg) was without effect upon the action of the antiepileptic drugs tested. Finally, none of the calcium channel inhibitors studied influenced the action of diazepam (0.2 mg/kg). It may be concluded that combinations of ethosuximide, with either nifedipine or diltiazem, may be promising for the treatment of absence epilepsy.