This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Heard, K Articles by Zahniser, N. Search for Related Content PubMed PubMed Citation Articles by Heard, K Articles by Zahniser, N. Social Bookmarking                   What's this?

Administration of ziprasidone for 10 days increases cocaine toxicity in mice

Department of Surgery, Division of Emergency Medicine, University of Colorado School of Medicine, Denver, Colorado, USA; Denver Health and Hospitals, Rocky Mountain Poison and Drug Center, Denver, Colorado, USA Kennon.Heard{at}RMPDC.org

S Krier

University of Colorado School of Medicine, Denver, Colorado, USA

NR Zahniser

Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado, USA

Long-term treatment with antipsychotic medications alters the regional density of several of the neurotransmitter receptors that mediate cocaine toxicity. However, the effect of either up- or down-regulation of the neurotransmitter receptors on cocaine toxicity is unknown. In this study, we determined if subacute administration of the atypical antipsychotic ziprasidone altered the toxic effects of cocaine in mice. Ziprasidone (4 mg/kg) or placebo was administered to the first two groups of CF-1 mice for 10 days and, then on day 10, an estimated LD50 dose of cocaine (102 mg/kg) was given to these mice. In a third group, in order to produce a ziprasidone withdrawal state, we administered ziprasidone for 10 days, followed by no treatment for 2 days before cocaine administration. There was no significant difference among the three groups in overall survival: 63% in the treatment group, 60% in the withdrawal group, and 80% in the placebo group. Survival time was significantly shorter for the withdrawal group than for the control group. Our study may have been limited by lower than expected serum ziprasidone concentrations and lower than expected lethality from cocaine. However, our findings suggest that administration of an atypical antipsychotic for 10 days may increase the toxic effects of cocaine.

Key Words: cocaine • drug interaction • ziprasidone

Human & Experimental Toxicology, Vol. 27, No. 6, 499-503 (2008)
DOI: 10.1177/0960327108095471


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?