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

娱乐性使用摇头丸，或（±）- 3,4 -亚甲基二氧甲基苯丙胺（MDMA），通常与其他药物有关，其中乙醇是舞蹈俱乐部和锐舞文化中最常见的药物之一。研究了乙醇共给药对雄性sd大鼠MDMA药代动力学和体温的影响。分别腹腔注射10、30 mg/kg MDMA和1.5 g/kg乙醇给药大鼠MDMA血浆浓度-时间谱。MDMA给药后4 h处死大鼠，取血浆和脑组织。采用气相色谱-质谱联用（GC-MS）对血浆和脑组织样品进行分析。两种浓度给药后10 ~ 20 min均出现MDMA血药浓度峰值（C_<max>）。乙醇与MDMA联用使血浆中MDMA浓度显著高于单用MDMA （p<0.05）。乙醇灌胃后，20 min时C_<max>约为1.6 mg/ml， 4 h后未检测到C_<max>。双室开体模型充分描述了MDMA在大鼠体内的处置动力学。4 h后，四组大鼠脑内MDA和MDMA浓度无显著差异，MDA是MDMA的主要代谢物。采用气相色谱-质谱分析。MDMA和MDA与乙醇一起很好地分布在大脑中。单独注射乙醇后温度下降，注射MDMA后温度升高。乙醇联合用药条件下MDMA效应的增强可能是由于MDMA血浆浓度最初升高，随后MDMA在脑内的作用增强，这可能解释了乙醇联合用药条件下MDMA效应增强的原因。

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.