Cocaine toxicity and the calcium channel blockers nifedipine and nimodipine in rats

Two dihydropyridine type calcium channel blockers (CCBs) were studied for any protective or therapeutic effect upon cocaine-induced toxicity and death in rats. To test for the protective effects, rats were pretreated with vehicle (control), nifedipine or nimodipine, intraperitoneally (IP) 30 minutes prior to an LD₈₅ of cocaine, or intravenously (IV) 10 minutes prior to cocaine administration. Anumals receiving EP control vehicle developed seizures in 5.6 ± 1.0 minutes and respiratory arrest in 9.8 ± 1.4 minutes. Animals pretreated EP with nifedipine or nimodipine developed seizures and respiratory arrest significantly sooner than the controls, although the overall incidences of seizures and respiratory arrest were not significantly different. Pretreatment with IV CCBs resulted in similar findings. To test the therapeutic effect of CCBs given following cocaine overdose, rats were administered cocaine EP and then treated with IV nifedipine or nimodipine once seizures occurred. In these animals, there was no significant difference in the Incidence or time to respiratory arrest compared to vehicle controls. This study demonstrates that neither pretreatment nor posttreatment with the CCBs nifethpine or nimodipine reduces cocaine toxicity in this rodent model.