Antiepileptic Effects of a Calcium Antagonist (Nimodipine) on Cefazolin‐Induced Epileptogenic Foci in Rabbits

Abstract

The epileptogenic properties of cefazolin (CFZ) were utilized to induce an electrophysiological pattern of epilepsy in the rabbit. CFZ, cortically applied in different concentrations (2 or 4%), produced epileptic activity in a degree proportional to the concentration of the substance. In this experimental epilepsy model, we evaluated the effects of increasing doses (0.025, 0.05, and 0.1 mg/kg i.v.) of the calcium antagonist nimodipine (Bay e 9736). In the evaluation of nimodipine effects, the spike-and-wave burst frequency per minute was taken into account. These data were compared with those of placebo-treated (Bay e 9736 control test) control groups and statistically evaluated by two-tailed t test. In 2% CFZ-induced epilepsy, nimodipine at the 0.025- and 0.05-mg/kg doses did not produce significant changes in the EEG pattern. A statistically significant reduction (p less than 0.001) in epileptic activity was observed at the 0.1-mg/kg nimodipine dose. This reduction was seen first in the contralateral focus leads and persisted for the entire time of observation. In the more intense epileptic form (4% CFZ), nimodipine at the doses employed did not induce noteworthy EEG modifications. These data indicate that nimodipine exerts an antiepileptic effect. The possible mechanisms involved in this activity of a calcium antagonist are discussed.

Effects of Ca2+antagonists on glutamate release and Ca2+influx in the hippocampus with in vivo intracerebral microdialysis

“…This may form the basis of seizures induced by Quin. Therefore, Ca2+ channels in cell soma rather than in nerve terminals were responsible for this disorder, because nimodipine can inhibit Quin-induced seizures (Morocutt et al, 1986;Lu et al, 1990). In these studies, no correlations were found between blocking Ca2 + influx and seizures induced by Quin, even with large doses of daurisoline.…”

Differential effects of valproic acid and enzyme‐inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients.

“…Apart from its vascular action, nimodipine is known to be a potent antagonist of transmembrane calcium influx in cerebral neurons. Since disturbances in neuronal calcium conductance have been implicated in the generation and propagation of seizure activity (Schmidt & Ried, 1989), many investigators have assessed the potential anticonvulsant action of nimodipine in animal models, demonstrating that the drug is effective in preventing and/or supressing seizures induced by a wide variety of chemical (Dolin et al, 1986;Meyer et al, 1987;Morocutti et al, 1986;Paczynsky et al, 1990) and physical (De Sarro et al, 1988;Meyer et al, 1990) stimuli. Preliminary clinical observations support the hypothesis that nimodipine may exert valuable therapeutic effects in patients with seizure disorders (Brandt et al, 1988;De Falce et al, 1989).…”

Epileptogenic Activity of Methicillin-Resistant Staphylococcus aureus (MRSA) Antibiotics in Rats

“…On the hand, Morocutti et al 18) reported that the intravenous injection of calcium antagonist, nimodipine, showed the significant inhibition of the cefazolin-induced epileptogenic foci in rabbits. In addition, nimodipine prevented penicillin-induced seizures in rats.…”