OPIOID DRUG DISCRIMINATION

阿片类药物歧视

基本信息

批准号：
2012864
负责人：
GEORGE BIGELOW
金额：
$ 30.73万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-08-01 至 1998-12-31
项目状态：
已结题

项目摘要

This is a proposal to continue an ongoing and productive clinical research project using drug discrimination procedures in human volunteers to characterize the discriminative stimulus characteristics, the subjective, behavioral, and physiological effects, and the profile of opioid receptor activity of various opioids. Attention is directed especially to the opioid mixed agonist-antagonists. These studies are conducted in a well- control led and supervised residential laboratory where the effects of the drugs can be carefully assessed, and where volunteers remain stable and well cared for. In the drug discrimination procedure, volunteers are trained to recognize specific reference drugs and then are tested with novel drugs or doses to assess their similarity to these known standards. Behavioral discrimination data are collected concurrently with subjective effects data, physiological data, and psychomotor/cognitive performance data. The studies provide important data about the opioid receptor mechanisms through which the various opioids produce their effects, about the cross-species generality to humans of the extensive drug discrimination data from preclinical laboratory research, about the relationship between subjective and discriminative drug effects, and about the influence and application of procedural variations in the behavioral drug discrimination procedure itself. Twelve studies are proposed. Three studies will investigate the effect of mu-receptor antagonism with naltrexone on the effects of pentazocine, nalbuphine, and butorphanol. Three studies will investigate the effect of kappa-receptor antagonism with buprenorphine on the effects of pentazocine, nalbuphine, and butorphanol. Other studies will investigate: (1) adaptation of the drug discrimination procedure to characterize the time course of alternative dosage forms of fentanyl and of morphine; (2) the utility of a within- session dose-effect assessment procedure for enhancing the speed and efficiency of human drug discrimination research; (3) the effect of opioid tolerance on response to hydromorphone and butorphanol; (4) the stimulus similarity of mixed agonist-antagonists to sedative drugs; (5) the comparative response of males versus females to opioids; and, (6) whether drug use and community functioning change following clinical pharmacology research participation.

这是继续进行持续且富有成效的临床研究的建议在人类志愿者中使用药物歧视程序的项目表征歧视性刺激特征，主观，行为和生理效应以及阿片受体的特征各种阿片类药物的活性。注意特别关注阿片类混合激动剂 - 抗逆邦剂。这些研究是在一个很好的控制LED和监督住宅实验室的影响可以仔细评估毒品，志愿者保持稳定和很好的照顾。在药物歧视程序中，志愿者是经过训练以识别特定的参考药物，然后接受测试新型药物或剂量以评估其与这些已知标准的相似性。行为歧视数据与主观同时收集效果数据，生理数据和精神运动/认知表现数据。研究提供了有关阿片类药物受体的重要数据各种阿片类药物产生其作用的机制，大约广泛药物的人类的跨物种一般性临床前实验室研究的歧视数据，关于主观和歧视性药物作用之间的关系，以及过程变化在行为中的影响和应用药物歧视程序本身。提出了十二项研究。三研究将研究MU受体拮抗作用纳曲酮对五唑胺，纳布汀和丁苯酚的影响。三项研究将研究Kappa受体拮抗作用丁丙诺啡对五唑胺，纳布丁和丁醇。其他研究将研究：（1）适应药物歧视程序以表征替代的时间过程芬太尼和吗啡的剂型；（2）一个内部的效用会话剂量效应评估程序，以提高速度和人类药物歧视研究的效率；（3）阿片类药物的作用对水电和丁香醇的反应的耐受性；（4）刺激混合激动剂 - 抗逆邦剂与镇静药物的相似性；（5）男性与女性对阿片类药物的比较反应；以及（6）是否临床药理学后的药物使用和社区功能变化研究参与。