DOSE-RESPONSE RELATIONSHIPS WITH NIMODIPINE AGAINST ELECTROSHOCK SEIZURES IN MICE

The anticonvulsant effect of the dihydropyridine calcium channel block er, nimodipine (NMD) was evaluated against electroshock-induced seizur es in mice. At 1 h postdosing, NMD elicited a dose-dependent reduction in the occurrence of tonic hindlimb extension (THE) after maximal ele ctroshock (MES). The calculated ED,, for NMD was 87 mg/kg. A single do se of NMD (75 mg/kg) produced a significant (p < 0.05) reduction in oc currence of THE for less than or equal to 12 h postdosing. NMD was det ectable for less than or equal to 6 h, and plasma and brain drug conce ntrations correlated well (r = 0.677, p < 0.01) for that period. At 1 h postdose, a single dose of NMD (75 mg/kg) produced a 40% increase (p < 0.001) in the threshold for tonic seizures as determined by minimal electroshock (Min-ES). NMD is an effective anticonvulsant against exp erimental seizures induced by electroshock. The pharmacodynamic effect of NMD appears to extend beyond the time anticipated from the pharmac okinetic profile.