Dose-response relationships with nimodipine against electroshock seizures in mice.
The anticonvulsant effect of the dihydropyridine calcium channel blocker, nimodipine (NMD) was evaluated against electroshock-induced seizures in mice. At 1 h postdosing, NMD elicited a dose-dependent reduction in the occurrence of tonic hindlimb extension (THE) after maximal electroshock (MES). The calculated ED50 for NMD was 87 mg/kg. A single dose of NMD (75 mg/kg) produced a significant (p < 0.05) reduction in occurrence of THE for < or = 12 h postdosing. NMD was detectable for < or = 6 h, and plasma and brain drug concentrations 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 experimental seizures induced by electroshock. The pharmacodynamic effect of NMD appears to extend beyond the time anticipated from the pharmacokinetic profile.
Sills
G J
GJ
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
Carswell
A
A
Brodie
M J
MJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D008297:Male; D051379:Mice; D009553:Nimodipine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*
D000927:Anticonvulsants; D009553:Nimodipine