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. Animals receiving IP control vehicle developed seizures in 5.6 +/- 1.0 minutes and respiratory arrest in 9.8 +/- 1.4 minutes. Animals pretreated IP 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 IP 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 nifedipine or nimodipine reduces cocaine toxicity in this rodent model.