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Dose‐Response Relationships with Nimodipine Against Electroshock Seizures in Mice
Author(s) -
Sills G. J.,
Carswell A.,
Brodie M. J.
Publication year - 1994
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1994.tb02457.x
Subject(s) - dihydropyridine , nimodipine , anticonvulsant , pharmacology , pharmacokinetics , pharmacodynamics , chemistry , ed50 , epilepsy , anesthesia , medicine , calcium , receptor , psychiatry
Summary: 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 ED 50 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 12 h postdosing. NMD was detectable for 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.