Influence of calcium channel inhibitors upon the anticonvulsant efficacy of common antiepileptics against pentylenetetrazol-induced convulsions in mice

• Published in: Neuropharmacology Vol. 29; no. 10; p. 943
• Main Authors: Czuczwar, S J, Małek, U, Kleinrok, Z
• Format: Journal Article
• Language: English
• Published: England 01-10-1990
• Subjects: Animals; Anticonvulsants - therapeutic use; Calcium Channel Blockers - therapeutic use; Diltiazem - pharmacology; Drug Therapy, Combination; Ethosuximide - therapeutic use; Male; Mice; Nifedipine - therapeutic use; Pentylenetetrazole; Phenobarbital - therapeutic use; Reference Values; Seizures - chemically induced; Seizures - drug therapy; Seizures - physiopathology; Valproic Acid - therapeutic use; Verapamil - therapeutic use
• ISSN: 0028-3908
• DOI: 10.1016/0028-3908(90)90145-H

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.