MDMA在染毒家兔体内的分布

目的:观察3,4-亚甲基二氧基甲基苯丙胺(MDMA)染毒家兔生命体征变化,并对急死与延缓死亡动物体内药物分布进行研究。方法:家兔以10 mg·kg-1剂量灌胃(ig)给予MDMA,BL-5生物机能实验系统记录从开始给药到动物被处死前的心电、血压和呼吸等主要生命体征变化;分别于给药2 h和6 h处死动物,采用气-质联用(GC/MS)法测定组织及体液中MDMA浓度。结果:家兔给药后,四肢出现间歇性震颤,血压升高,呼吸与心率加快,1 h左右达到高峰,之后缓慢下降;给药2 h后体内器官组织中药物浓度高于体液,其中以胃内容、肺及脾含量最高,6 h后组织与血液中药物浓度明显下降,而胆汁与尿液中药物浓度基本不变,胆汁中药物浓度高于其他组织。结论:尿液为鉴定MDMA滥用的最佳检材;对滥用MDMA死亡者脏器组织与体液中药物含量测定,可对用药后急死或延缓死亡做出判断。     

MDMA在急性中毒大鼠体内的分布研究

目的:建立3,4-亚甲基二氧基甲基苯丙胺(MDMA)大鼠急性中毒模型,研究MDMA在大鼠体内的分布情况。方法:按30mg·kg-1给予实验大鼠MDMA盐溶液,灌胃(ig),2h后脱臼处死。运用乙醚萃取衍生化法和气/质联用技术(GC/MS),对大鼠体内各组织和血液中的MDMA进行定性定量分析。结果:急性中毒大鼠体内各组织和血液中MDMA浓度大小依次是:脾>胃>肺>肝>肾>脑>心肌>心血。结论:MDMA广泛分布于大鼠体内各组织及血液中,对这些组织均有潜在的毒害。     

MDMA在急性染毒大鼠死后体内的再分布

目的:探索死后MDMA再分布变化规律及温度对死后MDMA再分布的影响。方法:将急性染毒大鼠处死后,分别置于室温下(17℃)或冷藏(4℃)。并于死后0 h2、h、24 h、48 h采集心血、外周血及心肌、肝、脾、肺组织,用液-液萃取衍生化法和气相色谱-氮磷检测器(GC-NPD)检测MDMA含量。结果:大鼠死后48 h内,随死亡时间延长,室温下心血MDMA浓度呈升高趋势(P<0.05),肝MDMA浓度先升后降(P<0.05),心肌MDMA浓度无显著性变化(P>0.05)。在死后2-24 h内,脾MDMA浓度升高(P<0.05),肺MDMA浓度下降(P<0.05)。冷藏下血液中MDMA变化幅度较小(P<0.01);组织MDMA浓度在室温和冷藏下比较差异无显著性(P>0.05)。结论:MDMA在大鼠体内存在死后再分布现象,死后血药浓度在低温下较高温下稳定。     

GC/MS法同时检测生物样品中苯丙胺、甲基苯丙胺及MDMA

目的:建立体液和组织中苯丙胺、甲基苯丙胺和3,4 -亚甲基二氧基甲基苯丙胺(MDMA)的简便快速、灵敏可靠的GC/MS检测方法。方法:样品经碱化,乙醚提取,TFA衍生化后,GC/MS全扫描定性检测,选择离子扫描(SIM)定量分析。结果:几种药物在血浆中的线性范围为0 .0 2 - 2 . 0 μg·ml-1,最低检出浓度为0 . 0 0 5 μg·ml-1(S/N≥3) ;肝脏中线性范围为0 . 0 5 - 5. 0 μg·g-1,最低检出浓度0. 0 .10 μg·g-1(S/N≥3)。相关系数大于或等于0 9980 ;回收率在92. 1% - 10 5. 2 %之间。结论:GC/MS方法适用于生物样品中苯丙胺、甲基苯丙胺和MDMA浓度的检测。     

苯丙胺类兴奋剂滥用后性行为及相关性行为特征变化的流行病学调查

目的獉獉:调查我国苯丙胺类兴奋剂滥用人群特征及滥用后性行为及相关性行为特征的变化。方法獉獉:采用回顾性自身前后对照设计,以课题组自拟调查问卷为工具,对符合调查对象入选要求、且甲基苯丙胺或3,4-亚甲基二氧甲基苯丙胺尿液毒品检测阳性的调查对象进行调查。结果獉獉:本调查共收集有效问卷394份,调查对象中75.1%为男性,20-30 a和30-40 a所占的比例分别为47.2%和35.0%。滥用涉及各类群体,但以私营或个体劳动者(31.9%)和无业(41.7%)为主。调查对象的中位累计滥用时间为8个月,主要滥用方式为烫吸(97.7%)。苯丙胺类兴奋剂滥用后性活动变化明显,表现为出现性冲动(63.5%)、性欲增强(35.0%)、性活动频率增加以及性活动持续时间延长(61.3%)等现象。调查结果还表明20.8%的调查对象滥用苯丙胺类兴奋剂后经常发生性行为,9.0%几乎每次都发生,分别有36.1%和21.7%的调查对象会与一起用药的人、性服务工作者发生性关系。此外,8例调查对象报告与同性发生过性关系;6例报告发生过性暴力;6例报告发生过性交易。按照性别和滥用剂量进行分层分析后发现,男性与女性在滥用苯丙胺类兴奋剂后的性行为及性行为相关特征有一定差异。结论獉獉:苯丙胺类兴奋剂滥用后性活动变化明显,提示苯丙胺类兴奋剂滥用对性行为可能有刺激作用。另外,男性和女性在滥用后均表现出性兴奋的特征,但男性的性活动比女性更活跃。对不同滥用剂量分组后进行相关性行为差别的分析分层分析[B1]结果提示苯丙胺类兴奋剂滥用与对性行为的刺激作用之间可能存在一定的剂量-反应关系。本研究的结论均来自患者自我报告,尚需进一步研究证实。     

MDMA诱导大鼠神经元凋亡及凋亡相关因子caspase-3的表达

目的 探讨3,4 -亚甲基二氧基甲基苯丙胺(MDMA)对实验大鼠神经元凋亡的诱导及凋亡相关因子半胱氨酸天冬氨酸特异性蛋白酶-3(caspase-3)的表达.方法 将20只Wistar雄性大鼠随机均分为1组对照组(A)、3组MDMA实验组(B、C、D).B组予MDMA(20 mg · kg-1, ip, single),C组予MDMA(20 mg · kg-1, 8 am,8 pm,ip×2 d),D组予MDMA (20 mg · kg-1 ,8 am,8 pm,ip×4 d);A组给予等体积生理盐水.采用TUNEL法检测神经元凋亡,免疫组织化学方法检测Caspase-3的表达.结果 给予MDMA后,大鼠各相关脑区有凋亡细胞形成,Caspase-3有不同程度的表达.结论 MDMA可导致神经元的凋亡,并诱导凋亡相关因子Caspase-3的表达.     

MDMA诱导神经元凋亡与细胞色素C表达的研究

目的探讨3,4-亚甲基二氧基甲基苯丙胺(MDMA)诱导大鼠神经元凋亡与细胞色素C(Cyt C)的表达。方法MDMA对照组采用生理盐水,用TUNEL法检测神经元凋亡,免疫组织化学方法检测CytC的表达。结果给予MDMA后,大鼠各脑区有凋亡细胞形成,Cyt C有不同程度的表达。结论MDMA可导致神经元的凋亡,并诱导凋亡相关因子Cyt C的表达。     

甲基苯丙胺的神经毒性及对GFAP表达的研究

目的探讨甲基苯丙胺(MA)的神经毒性及胶质纤维酸性蛋白(GFAP)的表达。方法设立对照组和实验组,实验组予MA,对照组予等体积生理盐水。采用HPLC测定不同脑区DA和5-HT的含量,用免疫组织化学方法检测GFAP的表达。结果给予MA后,大鼠额叶皮层和纹状体的5-HT和DA均有下降;但对海马DA的影响不明显,对GFAP蛋白的表达明显上调。结论MA对中枢5-HT、DA系统具有明显的神经毒性,并导致GFAP表达的上调。     

3,4-亚甲基二氧基甲基苯丙胺对大鼠的神经毒性及维生素C的保护作用

目的:探讨3,4-亚甲基二氧基甲基苯丙胺(MDMA)的神经毒性机制及抗氧化剂维生素C是否具有MDMA神经毒性的保护作用.方法:雄性Wistar大鼠随机分为正常对照组、MDMA组、MDMA给药前30 min给予维生素C组、MDMA给药后3 h给予维生素C组、MDMA给药后5 h给予维生素C组,MDMA和维生素C均为单剂量腹腔注射,剂量分别为20和250 mg·kg-1.1周后采用高效液相色谱法测定海马、枕叶皮层5-羟色胺(5-HT)的含量,原位杂交方法检测SERTmRNA,免疫组织化学法检测GFAP蛋白.结果:与正常对照组比较,MDMA组大鼠枕叶皮层、海马5-HT含量均明显下降(P<0.05),大鼠海马SERTmRNA的表达明显下降(P<0.05),而脑组织GFAP蛋白的表达显著升高(P<0.05).与MDMA组比较,提前30 min和MDMA后3 h给予维生素C两组的5-HT含量和海马SERTmRNA的表达无明显改变(P>0.05),而给予MDMA后5 h给予维生素C组的5-HT含量和海马SERTmRNA的表达明显增加(P<0.05);不同时间给予维生素C的3组大鼠脑组织GFAP蛋白的表达均较MDMA组显著降低(P<0.05).结论:MDMA对中枢5-HT系统具有明显的神经毒性;在给予MDMA后5 h给予维生素C对5-HT能系统有保护作用.     

武汉市近三年收缴的毒品情况分析

目的:通过分析武汉市近3年收缴的毒品,了解武汉市的毒品市场和毒品流行情况。方法:对武汉市公安局毒品检测中心保管的2004年-2006年全市收缴的毒品种类和数量以及相关案件进行统计分析。结果:从2004年到2006年,海洛因的收缴数量从37935.4g下降到8778.22g;MDMA的收缴数量从8792.67g下降到19.99g;甲基苯丙胺的收缴数量从7718.79g上升到27118.47g;氯胺酮的收缴数量从23950.67g上升到105565.88g。结论:收缴的海洛因和MDMA数量大幅减少,甲基苯丙胺稳定增长,氯胺酮明显增多。建议加大对制贩新型毒品的处罚力度和对娱乐场所的管理力度。     

MDMA and 5-HT neurotoxicity: the empirical evidence for its adverse effects in humans - no need for translation

In this issue of the BJP, Green et al. suggest that animal data could not be used to predict the adverse effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans and that MDMA did not produce 5-HT neurotoxicity in the human brain. This proposal was, however, not accompanied by a review of the empirical evidence in humans. The neuroimaging data on 5-HT markers in abstinent recreational ecstasy/MDMA users are extensive and broadly consistent. Reduced levels of the 5-HT transporter (SERT) have been found by research groups worldwide using a variety of assessment measures. These SERT reductions occur across the higher brain regions and remain after controlling for potential confounds. There are also extensive empirical data for impairments in memory and higher cognition, with the neurocognitive deficits correlating with the extent of SERT loss. Hence, MDMA is clearly damaging to humans, with extensive empirical data for both structural and functional deficits.     

甲基苯丙胺类混合物-摇头丸滥用方式及其对精神活动的影响

了解甲基苯丙胺类混合物滥用者的滥用模式及其对精神活动的影响。方法··:用GC -MS方法对当场截获的毒品成分进行检测 ,以问卷方式收集滥用者的滥用方式、滥用后的主观感受和行为表现。结果··:被称为“摇头丸”的主要成分为甲基苯丙胺和MDMA的混合物 ,并掺有杂质。被调查者平均年龄24.80a±s3.98a ,滥用场所均为周末或朋友聚会时的舞厅 ,平均滥用剂量为每次0.36±s0.12片 (每片约250mg),多数随啤酒送服。每周使用2次者占23.8 %。“摇头丸”的作用时间为4.58h±s5.17h。滥用后主要感受有愉快心境、体力充沛、亲密感增强 ;主要行为表现有随音乐摇摆 ,活动增多和磨牙等。“摇头丸”作用消失后部分滥用者感到疲乏、焦虑和渴求等 ,但未见明显戒断症状。结论··:甲基苯丙胺类物质的滥用趋势及长期使用后对健康的不良影响不容忽视。     

慢性甲基苯丙胺中毒大鼠和人血清中硝基化损伤水平及其神经毒性的研究

目的:通过观察慢性甲基苯丙胺中毒大鼠及长期甲基苯丙胺依赖人类血清中3-NT的含量变化,间接反映体内ONOO-的含量变化,探讨甲基苯丙胺导致蛋白质硝基化参与的神经毒性机制。方法:建立慢性甲基苯丙胺中毒大鼠模型,收集甲基苯丙胺长期依赖者血清与未吸毒的正常人血清;ELISA检测大鼠及人血清内3-NT的含量。结果:与对照组相比,甲基苯丙胺组大鼠和人血清中3-NT含量明显增多,差异有统计学意义(P<0.001)。结论:慢性甲基苯丙胺中毒动物和长期毒品依赖者血清的3-NT含量增高,表明其所代表的关键蛋白的硝基化参与了甲基苯丙胺的神经毒性作用。     

FUNCTION IN NEUROTOXICITY: INDEX OF EFFECT AND ALSO DETERMINANT OF VULNERABILITY

1. In neurotoxicity, functional indices may be the only available measures of effect, as many potent neurotoxic agents produce no morphological change. Examples of these are strychnine, dieldrin and pyrethroids, which produce excitation but no pathology, and barbiturates, xylene and lithium, which produce depression but no pathology. 2. In other cases where both functional and morphological effects are seen, functional measures often produce the most convenient, if not always the most specific, indices of toxicity. Appropriate functional measures can be highly sensitive, both in humans and in experimental animals, and can also give vital mechanistic information. However, it is essential that functional measures are reproducible and interpretable (some behavioural measures are not) and also provide a reasonably exacting test of function (passive observation of resting behaviour can miss many effects). 3. In addition to their use as an index of toxicity, changes in function, even within the normal range, can themselves influence susceptibility to toxins. Tissue perfusion can determine delivered dose and is influenced by function, while metabolic transformation is modified by nutritional state. Nutritional state can also influence absorption, with anaemia enhancing manganese toxicity and calcium deficiency enhancing lead toxicity. Functional activity can influence target susceptibility directly: thus, noise exposure enhances the ototoxicity of carbon monoxide, toluene or aminoglycoside antibiotics; noise, motor activity or anaesthesia all influence the central neurotoxicity of dinitrobenzene or metronidazole; motor activity enhances the peripheral nerve toxicity of lead or thallium; and nerve regeneration enhances the toxicity of hexane. These functional factors can be very important in determining individual susceptibility.     

VALIDATION AND IN VITRO NEUROTOXICITY

1. Validation of in vitro systems for studying neurotoxicants generally has not been accomplished, although in vitro tests have been used as screens to identify potential neurotoxic hazards and to study mechanisms. 2. A number of factors need to be taken into account when a test is validated: (i) a rationale for developing the test; (ii) clear biological or pathophysiological relevance of the endpoint to the effect detected in vivo; (iii) a standardized protocol and evidence of intra- and interlaboratory reproducibility; (iv) testing of chemicals representative of the categories of interest, including very toxic, moderately toxic and relatively non-toxic substances; and (v) a method to statistically evaluate the data. 3. Proper validation should lead to methods which can be used by regulatory agencies to make decisions regarding hazard/risk.     

Subjective ratings of prospective memory deficits in MDMA ('ecstasy') users

Chronic use of MDMA (3,4-methylenedioxymethamphetamine), or 'ecstasy', is associated with significant cognitive impairments, particularly in laboratory and field tests of memory for previously encoded material. Less is known about the effects of a history of MDMA use on aspects of everyday cognitive functioning-of which prospective memory (typically characterised as 'remembering to do something at some future point') is an important aspect. Self-ratings of prospective memory among 30 regular ecstasy users (taking the drug 10 or more times per month) and 31 ecstasy-free controls were compared. Each participant completed the Prospective Memory Questionnaire, which measures self-rated error frequencies relating to three aspects of prospective memory (short-term habitual, long-term episodic and internally cued); the scale also records the use of strategies to aid remembering. Compared with non-users, ecstasy users reported significantly more self-rated errors in prospective memory, an effect which was evident after co-varying levels of other drug use. There were no significant differences in the use of strategies to aid memory. These findings provide new insights into prospective memory dysfunction in recreational drug users. Prospective memory deficits may be related to the reported serotonergic and frontal lobe deficits in chronic MDMA users. It is necessary to use more objective tasks to assess putative prospective memory deficits in ecstasy users. Copyright 2001 John Wiley & Sons, Ltd.     

An in vitro approach to assessing a potential drug interaction between MDMA (ecstasy) and caffeine

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug which causes long-term neurotoxicity and increased risk of fatality. In rats, MDMA toxicity is exacerbated by co-administration of caffeine. The aim of this study was to investigate whether caffeine altered the effects of MDMA in a battery of in vitro tests selected to model some of the known actions of MDMA in vivo. In cytotoxicity studies, caffeine modestly enhanced the effect of MDMA on neuronal N2a cell viability but not that of liver, intestinal or kidney cells. MDMA inhibited the formation of fluorescent metabolites by CYP2D6 ≫ CYP3A4 > CYP1A2 but this was not altered by caffeine. Similarly, the inhibition of synaptosomal [³H] 5-HT uptake by MDMA was not affected by the presence of caffeine. Thus, these in vitro tests failed to detect any substantial interaction between caffeine and MDMA, highlighting the difficulty of modelling in vivo drug interactions using in vitro tests. However, the results show that the inhibition of synaptosomal [³H] 5-HT uptake by MDMA was greater at 41 °C and 25 °C than at 37 °C which raises the possibility that MDMA’s effect on SERT in vivo may be increased as body temperature increases, contributing to its harmful effects in users.     

MDMA神经毒性的长期效应对焦虑情绪的影响

目的:通过短时间多次给药建立神经毒性模型,在不同时间点采用多种行为学观察装置,观察大鼠的行为反应,探讨MDMA神经毒性对大鼠焦虑情绪的影响。方法:将♂Wistar大鼠随机分为对照组和实验组,实验组给予MDMA 10 mg·kg-1每小时一次,共4次,即总量为40 mg·kg-1,对照组给予等体积生理盐水。分别于末次给药后第2、8、26、32周末进行开场实验(open field test,OFT),高架十字迷宫(elevated plus-maze,EPM)、群居相互接触实验(social interaction test,SIT)。结果:短时间多次给予MDMA后,与生理盐水组比较,第2、8周末的开场实验、高架十字迷宫实验、群居相互接触实验未见焦虑相关行为增多(P>0.05)。第26、32周末时的上述实验发现焦虑相关行为明显增多(P<0.05)。结论:MDMA神经毒性的长期效应具有致焦虑作用。