Acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague-Dawley and Dark Agouti rats

被引：45

作者：

Malpass, A ^{[1
]}

White, JM ^{[1
]}

Irvine, RJ ^{[1
]}

Somogyi, AA ^{[1
]}

Bochner, F ^{[1
]}

机构：

[1] Univ Adelaide, Dept Clin & Expt Pharmacol, Adelaide, SA 5005, Australia

来源：

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR | 1999年 / 64卷 / 01期

关键词：

3,4-methylenedioxymethamphetamine (MDMA); body temperature; acute toxicity; locomotor activity; CYP2D1; polymorphism; Sprague-Dawley/Dark Agouti rat;

D O I：

10.1016/S0091-3057(99)00116-1

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

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 cytocrome 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-Daw ley 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. (C) 1999 Elsevier Science Inc.

引用

页码：29 / 34

页数：6

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