Assessment of propofol, midazolam and ziprasidone, or the combinations for the prevention of acute cocaine toxicity in a mouse model

Study objectiveTo evaluate the effects of pretreatment, midazolam (M), propofol (P), ziprasidone (Z), and two combinations of [(midazolam plus propofol (MP); midazolam plus ziprasidone (MZ)] in mice models in the prevention of seizures, and death due to acute cocaine toxicity.Methods180 male CF-1 mice were randomized to 6 groups (30/group) in this experimental study. The animals were administered intraperitoneal injections of M (2 mg/kg), P (25 mg/kg), Z (4 mg/kg), MP (2 mg/kg and 25 mg/kg) and MZ (2 mg/kg and 4 mg/kg) or saline (S) as a pretreatment. 10 min later, the mice were administered intraperitoneal injections of 105 mg/kg cocaine. The groups were observed for cocaine-induced seizure and lethality.ResultsThe MP and MZ combinations showed the highest protective effect in terms of seizure and lethality relative to P and S (p < 0.001). M and Z were found effective compared to P and S (p < 0.001). There were no significant differences among MP and MZ, however there were significant differences between MP and Z in terms of lethality (p = 0.05). There were no significant differences among MP, MZ, M and Z groups in terms of seizure (p > 0.05). No death was observed in the MP combination group. Seizure rate was observed o be least in the MZ group with respect to the other groups.ConclusionAccording to our particular mouse model, this study suggests that MP and MZ combinations may be more effective than M or Z only for the prevention of cocaine-induced seizure and lethality. However, P alone does not prevent cocaine-induced seizure and lethality.

► The treatment of cocaine toxicity is an important subject for emergency physicians. ► We investigated the effects of midazolam, propofol, ziprasidone on acute cocaine toxicity in mice. ► Midazolam + propofol and midazolam + ziprasidone may be more effective than single use.