INFLUENCE OF NICARDIPINE, NIMODIPINE AND FLUNARIZINE ON THE ANTICONVULSANT EFFICACY OF ANTIEPILEPTICS AGAINST PENTYLENETETRAZOL IN MICE

Among three calcium channel inhibitors, only nicardipine (10-40 mg/kg) significantly inhibited clonic seizures induced by pentylenetetrazol administered at its CD97 (convulsive dose 97%) of 81 mg/kg, subcutaneo usly. Nimodipine and flunarizine (both up to 80 mg/kg) did not suppres s pentylenetetrazol-induced clonic seizures per se. Co-administration of nicardipine (5 mg/kg) resulted in a significant enhancement of the protective potency of either ethosuximide (50 mg/kg) or valproate (100 mg/kg) against clonic seizures in this test. Similar effects were not ed in case of combined treatment of nimodipine (20-40 mg/kg) with thes e antiepileptics. On the contrary: flunarizine (up to 20 mg/kg) did no t modify the anticonvulsive action of these antiepileptic drugs. Moreo ver, none of the studied calcium channel inhibitors influenced the pro tective activity of clonazepam (0.01 mg/kg). The antiepileptic drugs, administered alone in above doses, were ineffective against pentylenet etrazol-induced clonic convulsions. In case of ethosuximide and valpro ate, the motor performance in the chimney test was worsened by co-admi nistration of nimodipine (40 mg/kg). We found no pharmacokinetic inter actions (at least in relation to the plasma levels of ethosuximide and valproate) that could explain the observed results. Thus. we conclude that a combination of some calcium channel inhibitors and antiepilept ic drugs may provide more efficient protection against experimental se izures which may bear a potential clinical significance.