| Acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague-Dawley and Dark Agouti rats. | |
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MedLine Citation:
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PMID: 10494994 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ingestion of MDMA ("ecstasy") by humans can cause acute toxicity manifested by hyperthermia and death. Demethylenation of MDMA is catalyzed by cytochrome P-450 2D6 (CYP2D6) and cytochrome P-450 2D1 (CYP2D1) in humans and rats, respectively, and is polymorphically expressed. It has been proposed that CYP2D6 deficiency may account for the unexplained toxicity of MDMA. The female Dark Agouti rat is deficient in CYP2D1, and serves as a model for the human poor metabolizer. We investigated thermogenic and locomotor actions of MDMA in adult female Sprague-Dawley (CYP2D1 replete) and Dark Agouti rats. MDMA (2, 5, and 10 mg/kg) and saline were injected subcutaneously at ambient temperatures of 22 and 31 degrees C. There was no difference in core temperature responses between the two rat strains. Hypothermia occurred in the first 30 min and temperature elevation thereafter. MDMA increased locomotor activity in Sprague-Dawley but not in Dark Agouti rats. However, MDMA had pronounced lethal effects at 31 degrees C ambient in the Dark Agouti rats only. We conclude that the poor metaboliser phenotype may predispose to lethality, but the mechanism is as yet unknown. |
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Authors:
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A Malpass; J M White; R J Irvine; A A Somogyi; F Bochner |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pharmacology, biochemistry, and behavior Volume: 64 ISSN: 0091-3057 ISO Abbreviation: Pharmacol. Biochem. Behav. Publication Date: 1999 Sep |
Date Detail:
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Created Date: 1999-10-21 Completed Date: 1999-10-21 Revised Date: 2008-10-10 |
Medline Journal Info:
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Nlm Unique ID: 0367050 Medline TA: Pharmacol Biochem Behav Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 29-34 Citation Subset: IM |
Affiliation:
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Department of Clinical & Experimental Pharmacology, University of Adelaide, SA, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Oxidoreductases Animals Aryl Hydrocarbon Hydroxylases* Body Temperature Regulation / drug effects Cytochrome P-450 CYP2D6 / metabolism Cytochrome P-450 Enzyme System / metabolism Female Hallucinogens / metabolism, toxicity* Motor Activity / drug effects N-Methyl-3,4-methylenedioxyamphetamine / metabolism, toxicity* Rats Rats, Sprague-Dawley Species Specificity |
| Chemical | |
Reg. No./Substance:
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0/Hallucinogens; 42542-10-9/N-Methyl-3,4-methylenedioxyamphetamine; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.1.-/Alcohol Oxidoreductases; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/Cyp2d1 protein, rat; EC 1.14.14.1/Cytochrome P-450 CYP2D6 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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