MECHANISM OF ACTION OF BUTORPHANOL

布托啡诺的作用机制

基本信息

批准号：
3212377
负责人：
Ing K. Ho
金额：
$ 12.95万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-05-01 至 1996-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3212377
关键词：
analgesics drug addiction drug tolerance drug withdrawal laboratory rat morphine naloxone narcotic antagonists opioid receptor psychopharmacology receptor binding

项目摘要

The objective of this project is to investigate the mechanism of butorphanol tartrate (STADOL)-induced pharmacological responses and to determine how tolerance to and physical dependence upon butorphanol develop. Butorphanol is a potent non-scheduled opioid analgesic, yet case reports of butorphanol abuse and studies reported in the literature and our laboratory have demonstrated that butorphanol also possesses a substantial physical dependence liability under certain circumstances. The proposed project is designed to systematically assess how butorphanol produces pharmacological responses and how different opioid receptors, e.g. mu-, delta-, and kappa-receptors, are involved in butorphanol tolerance and dependence. Morphine sulfate will be compared as a reference compound when appropriate. Six specific aims are proposed. They are: Aim I. Characterization of the development of tolerance to and physical dependence upon butorphanol using continuous intracerebroventricular (i.c.v.) infusion of butorphanol via osmotic mini-pumps. Aim II. Identification of the opioid receptors involved in development of tolerance to butorphanol using pharmacologic agents. Aim III. Identification of the opioid receptors involved in development of physical dependence upon butorphanol using pharmacologic agents. Aim IV. Studies of changes in binding characteristics of different opioid receptors during the development of tolerance to and physical dependence upon butorphanol. Aim V. Correlations of the role(s) of different opioid receptors in the development of tolerance to and physical dependence upon butorphanol by testing correlations between the results obtained pharmacologically and biochemically. Aim VI. Comparative studies of the phenomena of tolerance to and physical dependence upon butorphanol and of how butorphanol tolerance-dependence affects different opioid receptors during systemic administration (s.c.) of butorphanol. The proposed project should reveal the mechanism of action of butorphanol, assess the addictive potential of butorphanol, suggest certain precautions to be considered during usage of butorphanol, provide more rationale for the treatment of butorphanol abuse, and provide awareness of the abuse potential of butorphanol.

该项目的目的是研究其机制酒石酸布托啡诺 (STADOL) 诱导的药理反应确定对布托啡诺的耐受性和身体依赖性发展。布托啡诺是一种有效的非定期阿片类镇痛药，但情况布托啡诺滥用的报告以及文献和我们的研究报告实验室证明布托啡诺还具有显着的某些情况下的身体依赖责任。拟议的该项目旨在系统地评估布托啡诺的生产方式药理反应以及如何不同的阿片受体，例如亩-， δ 和 kappa 受体参与布托啡诺耐受和依赖性。硫酸吗啡将作为参考化合物进行比较合适的。提出了六项具体目标。他们是：目标 I. 耐受性和身体耐受性发展的特征使用连续脑室内注射对布托啡诺的依赖性 (i.c.v.) 通过微型渗透泵输注布托啡诺。目标二。鉴定参与发育的阿片受体使用药物对布托啡诺的耐受性。目标三。鉴定参与发育的阿片受体使用药物对布托啡诺产生身体依赖性。目标四。不同阿片类药物结合特性变化的研究耐受性和身体依赖性发展过程中的受体布托啡诺。目标 V. 不同阿片受体在发展对布托啡诺的耐受性和身体依赖性测试药理学结果和结果之间的相关性生物化学上。目标六。耐受现象和物理现象的比较研究对布托啡诺的依赖性以及布托啡诺的耐受性依赖性在全身给药（s.c.）期间影响不同的阿片受体布托啡诺。拟议的项目应揭示布托啡诺的作用机制，评估布托啡诺的成瘾潜力，建议采取某些预防措施在使用布托啡诺期间要考虑，提供更多理由治疗布托啡诺滥用，并提高人们对滥用情况的认识布托啡诺的潜力。