Dose-response relationships with nimodipine against electroshock seizures in mice

Epilepsia. 1994 Mar-Apr;35(2):437-42. doi: 10.1111/j.1528-1157.1994.tb02457.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants* / pharmacology
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Electroshock
  • Male
  • Mice
  • Nimodipine / administration & dosage
  • Nimodipine / pharmacokinetics
  • Nimodipine / pharmacology*
  • Seizures / etiology
  • Seizures / prevention & control*

Substances

  • Anticonvulsants
  • Nimodipine