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Simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates and interaction in the rat

大鼠体内麻黄碱、安非他明、可卡因、可卡因代谢物和阿片类药物的同时测定及其相互作用

基本信息

批准号：
17590585
负责人：
SAITO Takeshi
金额：
$ 0.9万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Recreational use of Ecstacy, or (±)-3, 4-methylenedioxymethamphetamine (MDMA), is often associated with other drugs, among which ethanol is one of the most common in the dance club and rave cultures. The effect of ethanol coadministartion on MDMA pharmacokinetics and body temperature was investigated in male Sprague-Dawley rats. MDMA plasma concentration-time profiles were characterized after intraperitoneal (i.p.) administration of 10 and 30 mg/kg MDMA alone and of MDMA with 1.5 g/kg ethanol to rats. Rats were sacrificed at 4 h after i.p. MDMA administration, and plasma and brain were collected. Plasma and brain samples were analyzed by gas chromatography-mass spectrometry (GC-MS). Following i.p. administration, the peak MDMA plasma concentration (C_<max>) were obtained 10-20 min after administration of both concentrations. Co-administration of ethanol with MDMA was significantly increased MDMA concentration in plasma than MDMA alone (p<0.05). Following i.p. ethanol dosing, C_<max> was about 1.6 mg/ml at 20 min, and it was not detected after 4 h. The disposition kinetics of MDMA in rats was adequately described by a two-compartment open body model. MDA and MDMA concentration in the brain were not different among the four groups after 4 h. MDA was a predominant metabolite of MDMA. It was also analyzed by GC-MS. MDMA and MDA are well distributed into the brain with ethanol. Although the temperature decreased after ethanol alone i.p. injection, it increased after MDMA i.p. injection. The enhancement of MDMA effects in the ethanol combination may be due to initially increased MDMA plasma concentration followed by the effect of MDMA in the brain, might explain the enhancement of MDMA effects in the ethanol combination condition.

摇头丸，或（±）-3，4-亚甲二氧基甲基苯丙胺（MDMA），经常与其他药物有关，其中乙醇是舞蹈俱乐部和锐舞文化中最常见的药物之一。在雄性Sprague-Dawley大鼠中研究了乙醇联合给药对MDMA药代动力学和体温的影响。在腹膜内（i. p.）对大鼠单独给予10和30 mg/kg MDMA以及MDMA与1.5 g/kg乙醇。腹腔注射MDMA后4 h处死大鼠，采集血浆和脑组织。通过气相色谱-质谱法（GC-MS）分析血浆和脑样本。腹膜内给药后，在两种<max>浓度给药后10-20分钟获得MDMA血浆峰浓度（C_）。乙醇与MDMA联合给药后，血浆中MDMA浓度显著高于MDMA单独给药（p<0.05）。腹膜内乙醇给药后，<max>20 min时C_约为1.6 mg/ml，4 h后未检测到C_。MDMA在大鼠体内的处置动力学可用二室开放体模型充分描述。脑组织MDA和MDMA含量在4 h后各组间差异无显著性。MDA是MDMA的主要代谢产物。GC-MS分析表明，乙醇作用下，MDMA和MDA在脑内分布均匀。虽然单独腹腔注射乙醇后体温降低，但腹腔注射MDMA后体温升高。乙醇联合给药中MDMA效应增强可能是由于MDMA血浆浓度最初升高，随后MDMA在脑中产生效应，这可能解释了乙醇联合给药条件下MDMA效应增强的原因。