新型滥用物质2C-B的毒理学及其代谢动力学研究

发布时间：2018-03-11 08:04

本文选题：2C-B　切入点：气相色谱法　出处：《哈尔滨商业大学》2012年硕士论文　论文类型：学位论文

【摘要】：2C-B(4-溴-2,5-二甲氧基苯乙胺)是一种具有致幻、兴奋作用的新型滥用物质,随着给药剂量的增加可对人体产生不同程度的精神作用。最近几年来在我国及周边地区频繁出现2C-B的身影,给人类社会造成严重危害,我们在与犯罪分子进行艰苦斗争的同时,也应对每种滥用物质进行深入研究,充分了解其在体内代谢过程及中毒成瘾机制,为2C-B吸食者的戒断和临床救治提供理论依据。本文首次对2C-B的毒理学和代谢动力学进行系统的实验分析,为2C-B及其系列毒品的进一步深入研究打下基础。主要研究内容及结果如下：通过2C-B对小鼠的急性毒性实验研究,确定LD100约为270mg/kg、LD0约为200mg/kg、LD50为234.11mg/kg,以此为长期毒性实验剂量选择提供依据。通过对雄性、雌性大鼠分别灌胃高、中、低三个剂量2C-B药液5个月,及停药1个月后脏器指数、血常规、血液生化学、组织病理学指标进行检测,进行2C-B对大鼠长期毒性实验研究。结果显示长期染毒对低剂量组影响微小,对高剂量组和中剂量组影响十分明显,机体出现的所有变化均主要与脑、心脏、肝脏、肺、肾产生病变关系紧密,且这些变化在1个月内基本不可恢复,提示这些脏器可能是2C-B毒性作用的靶器官,雌、雄无明显差异。论文对气相色谱测定血液中2C-B含量的方法进行系统评价,以质控样品计算,结果表明,该分析方法的专属性、线性关系、回收率、精密度、稳定性均良好,符合生物样品的测定要求。根据该方法测定不同时间点、不同给药剂量2C-B的血药浓度,数据经3P97药代动力学软件处理,得到相应的药代动力学参数,由结果可知雄性、雌性大鼠口服2C-B后,各剂量组测得的半衰期与剂量均无关,Cmax值和AUC值随剂量增大成倍增加,表明2C-B在给药剂量为10-40mg/kg范围内属于线性动力学,且符合一室模型。2C-B在雄性、雌性大鼠体内Ka、Ke、T1/2Ka、T1/2Ke、Tmax无明显差别；与雄鼠参数比较,雌鼠的AUC、Cmax值偏高,CL/f、V/f值偏低。通过上述实验结果,希望能为预防2C-B对机体损伤及不同性别2C-B滥用者的治疗提供参考依据。
[Abstract]:2C-BU 4- bromo-2-bromo-5-dimethoxyphenylethylamine) is a new type of substance of abuse with hallucinogenic and exciting effects. In recent years, 2C-B has frequently appeared in our country and its surrounding areas, causing serious harm to human society. While we are struggling hard with criminals, Each substance should also be thoroughly studied in order to fully understand its metabolic process in vivo and the mechanism of addiction to poisoning, To provide theoretical basis for the abstinence and clinical treatment of 2C-B users, the toxicology and metabolic kinetics of 2C-B were analyzed systematically for the first time. To lay the foundation for further study of 2C-B and its series of drugs. The main contents and results are as follows:. The acute toxicity of 2C-B to mice was studied. The results showed that the LD100 was about 270 mg / kg LD0 and about 200 mg / kg LD50 was 234.11 mg / kg, which provided the basis for the long-term toxicity experiment. The indexes of organ index, blood routine, blood biochemistry and histopathology of male and female rats were measured by intragastric administration of high, middle and low doses of 2C-B for 5 months and 1 month after withdrawal. The long-term toxicity of 2C-B to rats was studied. The results showed that the long-term exposure had little effect on the low dose group, and obvious effect on the high dose group and the middle dose group. All the changes in the body were mainly related to the brain, heart, liver and lung. The renal lesions were closely related, and these changes could not be recovered within one month, suggesting that these organs might be the target organs of 2C-B toxicity, but there was no significant difference between male and female. The method of determination of 2C-B in blood by gas chromatography was systematically evaluated and calculated by quality control sample. The results showed that the specificity, linear relationship, recovery rate, precision and stability of the method were all good. According to this method, the blood concentration of 2C-B was determined at different time points and dosages. The data were processed by 3P97 pharmacokinetic software, and the corresponding pharmacokinetic parameters were obtained. After oral administration of 2C-B in female rats, the half-life of each dose group was not related to the dose. The values of Cmax and AUC increased exponentially with the increase of dose, which indicated that 2C-B was linear kinetics in the range of dosage of 10-40 mg / kg, and was in accordance with one-compartment model .2C-B in male. There was no significant difference between female rats and female rats, but the AUC C max value of female rats was higher than that of male rats, and the V / f value of CLP / FV / f was lower in female rats than in male rats. Through the above experimental results, we hope to provide a reference for the prevention of 2C-B injury and the treatment of 2C-B abuser of different sex.
【学位授予单位】：哈尔滨商业大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.6

【参考文献】