Ziprasidone pretreatment attenuates the lethal effects of cocaine in a mouse model

Acad Emerg Med. 2005 May;12(5):385-8. doi: 10.1197/j.aem.2004.12.011.

Abstract

Background: Cocaine intoxication is a common cause of agitation in emergency department patients. Ziprasidone, an atypical antipsychotic, is being increasingly used for sedation of agitated patients in the emergency department.

Objectives: To provide preliminary animal data on the efficacy of ziprasidone for the treatment of acute cocaine poisoning.

Methods: This was a randomized, blinded comparison of ziprasidone and placebo for the prevention of seizures and apparent lethality in a mouse model of cocaine intoxication. Animals were assigned to either placebo or 0.4 mg/kg or 1.2 mg/m(2) of ziprasidone intraperitoneally 30 minutes prior to administration of 105 mg/kg of cocaine. Study outcomes were the proportions of animals having seizures and the apparent lethality.

Results: 1.2 mg/m(2) of ziprasidone decreased the lethal effects of cocaine by 50%, while 0.4 mg/kg decreased lethality by 13%. There was no effect on seizures at either dose.

Conclusions: Ziprasidone pretreatment decreased lethality in this mouse model of severe cocaine intoxication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Cocaine / poisoning*
  • Cocaine-Related Disorders / drug therapy*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Overdose
  • Injections, Intraperitoneal
  • Mice
  • Piperazines / therapeutic use*
  • Premedication
  • Random Allocation
  • Seizures / chemically induced
  • Seizures / drug therapy
  • Single-Blind Method
  • Survival Analysis
  • Thiazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Piperazines
  • Thiazoles
  • ziprasidone
  • Cocaine