3,4-亚甲基二氧甲基苯丙胺（“摇头丸”）及其对映体对单独饲养和拥挤饲养小鼠的致死率、核心体温和运动活动影响的药理学特征
Pharmacological characterization of the effects of 3,4-methylenedioxymethamphetamine ("ecstasy") and its enantiomers on lethality, core temperature, and locomotor activity in singly housed and crowded mice.
作者信息
Fantegrossi William E, Godlewski Tomek, Karabenick Rachel L, Stephens Jermaine M, Ullrich Thomas, Rice Kenner C, Woods James H
机构信息
Department of Pharmacology, University of Michigan, Medical School, 1301 MSRB III, Ann Arbor, MI 48109-0632, USA.
出版信息
Psychopharmacology (Berl). 2003 Mar;166(3):202-11. doi: 10.1007/s00213-002-1261-5. Epub 2003 Feb 1.
RATIONALE
Few studies have directly compared the effects of methylenedioxymethamphetamine (MDMA, "ecstasy") and its enantiomers across measures.
OBJECTIVES
To investigate the capacity of MDMA and its stereoisomers to produce aggregate toxicity in mice, the influence of 5-HT(2) receptors, 5-HT transporters, and ambient temperature on this effect, and to directly compare the racemate and its enantiomers in terms of their effects on core temperature and locomotor activity with and without various serotonergic pretreatments.
METHODS
Mice were injected with various doses of MDMA and its stereoisomers in various housing conditions, with and without pretreatments of serotonergic drugs, and at two distinct ambient temperatures; lethality was quantified 2 h after MDMA administration. For temperature/activity studies, mice were injected with various doses of MDMA and its enantiomers, with and without ketanserin, MDL100907, or fluoxetine pretreatments, and core temperature and locomotor activity data were collected for 24 h.
RESULTS
Racemic MDMA and its isomers produced aggregate toxicity in mice. The lethal effects of racemic MDMA and its enantiomers were differentially attenuated by the various serotonergic pretreatments and manipulation of the ambient temperature across housing conditions. Racemic and S(+)-MDMA produced hyperthermic effects in mice, while R(-)-MDMA did not. The pretreatment drugs attenuated the hyperthermic effects of racemic MDMA, but were less effective in blocking S(+)-MDMA-induced hyperthermia. Racemic MDMA and both enantiomers stimulated locomotor activity, although R(-)-MDMA was least effective. The pretreatments all reduced the locomotor stimulant effects of racemic MDMA but potentiated S(+)-MDMA-induced hyperlocomotion.
CONCLUSIONS
The MDMA isomers have heterogeneous effects that can be demonstrated across a wide range of endpoints.
理论依据
很少有研究直接比较3,4－亚甲基二氧甲基苯丙胺（摇头丸）及其对映体在各项指标上的影响。
目的
研究摇头丸及其立体异构体对小鼠产生综合毒性的能力、5-羟色胺（5-HT）2受体、5-HT转运体及环境温度对该效应的影响，并在有无各种5-羟色胺能预处理的情况下，直接比较外消旋体及其对映体对核心体温和运动活性的影响。
方法
在不同的饲养条件下，给小鼠注射不同剂量的摇头丸及其立体异构体，有无5-羟色胺能药物预处理，并在两个不同的环境温度下进行；给药后2小时对致死率进行量化。对于温度/活性研究，给小鼠注射不同剂量的摇头丸及其对映体，有无酮色林、MDL100907或氟西汀预处理，并收集24小时的核心体温和运动活性数据。
结果
外消旋摇头丸及其异构体对小鼠产生综合毒性。外消旋摇头丸及其对映体的致死效应因各种5-羟色胺能预处理及不同饲养条件下环境温度的改变而有差异地减弱。外消旋体和S(+)－摇头丸对小鼠产生体温过高效应，而R(－)－摇头丸则不会。预处理药物减弱了外消旋摇头丸的体温过高效应，但对阻断S(+)－摇头丸引起的体温过高效果较差。外消旋摇头丸及其两种对映体均刺激运动活性，尽管R(－)－摇头丸的效果最差。预处理均降低了外消旋摇头丸的运动刺激效应，但增强了S(+)－摇头丸引起的运动亢进。
结论
摇头丸异构体具有异质性效应，可在广泛的终点指标中得到证实。
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