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Ziprasidone, Diazepam, or the Combination for Prevention of Cocaine Toxicity in a Mouse Model

  1. Nathan R. Cleveland MD1,
  2. Shay Krier MD3,
  3. Kennon Heard MD2,*

Article first published online: 28 JUN 2008

DOI: 10.1197/j.aem.2007.04.012

Issue

Academic Emergency Medicine

Academic Emergency Medicine

Volume 14, Issue 8, pages 691–694, August 2007

Additional Information

How to Cite

Cleveland, N. R., Krier, S. and Heard, K. (2007), Ziprasidone, Diazepam, or the Combination for Prevention of Cocaine Toxicity in a Mouse Model. Academic Emergency Medicine, 14: 691–694. doi: 10.1197/j.aem.2007.04.012

Author Information

  1. 1

    Denver Health Residency in Emergency Medicine

  2. 2

    University of Colorado School of Medicine, Division of Emergency Medicine and the Rocky Mountain Poison and Drug Center

  3. 3

    University of Colorado School of Medicine (SK), Denver, CO

* Contact for correspondence and reprints: Kennon Heard, MD (Email: Kennon.heard@uchsc.edu).

Publication History

  1. Issue published online: 28 JUN 2008
  2. Article first published online: 28 JUN 2008
  3. Received March 1, 2007;Revised March 31, 2007;Revised April 3, 2007;Revised April 11, 2007;Revised April 15, 2007;Accepted April 16, 2007

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Keywords:

  • cocaine;
  • ziprasidone;
  • diazepam

BackgroundAcute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective.

ObjectivesTo assess whether the combination of these two medications would offer more protection than either treatment alone.

MethodsThis was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded.

ResultsAll treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02).

ConclusionsThis study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures.

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