Influence of flunarizine, nicardipine and nimodipine on the anticonvulsant activity of different antiepileptic drugs in mice.
Only flunarizine (40 mg/kg, i.p.) significantly raised the threshold for electroconvulsions in mice (ear-clip electrodes, 0.2 sec stimulus duration, tonic hindlimb extension as an endpoint), whilst nicardipine and nimodipine (up to 80 mg/kg) was ineffective in this respect. Further, flunarizine (10 and 20 mg/kg) potentiated the efficacy of carbamazepine and valproate against maximum electroshock (50 mA)-induced seizures and, in the dose of 20 mg/kg, enhanced that of diphenylhydantoin. In addition, this calcium channel inhibitor was without influence upon the total levels of these antiepileptics in plasma. Nicardipine (5 and 10 mg/kg) and nimodipine (10 and 20 mg/kg) increased the protective potential of carbamazepine and nimodipine (20 mg/kg) also decreased the ED50 of diphenylhydantoin against maximum electroshock. However, nicardipine distinctly increased the level of carbamazepine in plasma, whilst nimodipine did not affect the level of both antiepileptics in plasma. The combined treatment of calcium channel inhibitors and antiepileptic drugs, providing a 50% protection against maximum electroshock, did not significantly change the motor performance of mice in the chimney test, when compared with antiepileptic drugs, given alone at their ED50s, against maximum electroshock-induced convulsions. The present results give further support to the idea of the combined use of some calcium channel inhibitors and antiepileptic drugs in the treatment of human epilepsy.
Czuczwar
S J
SJ
Department of Pharmacology, Medical School, Lublin, Poland.
Gasior
M
M
Janusz
W
W
Kleinrok
Z
Z
D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology*; D004597:Electroshock; D005444:Flunarizine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009529:Nicardipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects
D000927:Anticonvulsants; D009553:Nimodipine; D009529:Nicardipine; D005444:Flunarizine