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

Abstract

Study objective: To 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. Methods: 180 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. Results: The 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. Conclusion: According 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. © 2012 Elsevier B.V.