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

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 (2mg/kg), P (25mg/kg), Z (4mg/kg), MP (2mg/kg and 25mg/kg) and MZ (2mg/kg and 4mg/kg) or saline (S) as a pretreatment. 10min later, the mice were administered intraperitoneal injections of 105mg/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.