MECHANISM OF ACTION OF BUTORPHANOL

布托啡诺的作用机制

• 批准号: 3212373
• 负责人: Ing K. Ho
• 金额: $ 8.47万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3212373
• 关键词: analgesics; drug addiction; drug addiction antagonist; drug metabolism; drug tolerance; drug withdrawal; laboratory rat; morphinans; naloxone; narcotics; opioid receptor

The goal of this project is to investigate the mechanisms of butorphanol-tratrate (STADOL)-induced pharmacological responses and to determine how tolerance to and physical dependence upon butorphanol develops. Butorphanol is classified as an agonist- antagonist narcotic analgesic which is stronger than morphine. Yet, butorphanol is exempted form control status. The studies reported in the literature have been conducted mainly following acute administration. The effects of continuous administration of butorphanol and its possible consequences (i.e., tolerance/ dependence) have not been adequately studies. Therefore, this project is designed to provide an animal model to systematically assess how butorphanol produces pharmacological responses and how butorphanol induces tolerance/dependence upon continuous administration. The evidence available at present is strongest for the involvement of different opioid receptors in the action of butorphanol. The following specific aims are designed to test the hypotheses formulated based on the rationale available. Four specific aims are proposed. They are: Aim I. Studies of the effects of acute butorphanol administration and their relationship to different opioid receptors. Aim II. Characterization of development of butorphanol using the model of continuous intracerebroventriculat (ICV) infusion of butorphanol via Osmotic Mini-pumps. Aim III. Characterization of development of butorphanol dependence. Aim IV. Characterization of the antagonistic properties of butorphanol in morphine dependent animals. The proposed systematic studies should (1) reveal the mechanism(s) of action of butorphamol, (2) provide awareness of the abuse liability of butorphanol, (3) suggest certain precautions to be considered during usage of butorphanol, (4) provide more rationale for the treatment of butorphanol abuse, and (5) identify the role(s) of different opioid receptors in the development of tolerance to and dependence on butorphanol.

该项目的目标是研究其机制 酒石酸布托啡诺 (STADOL) 诱导的药理反应和 以确定如何耐受和身体依赖 产生布托啡诺。 布托啡诺被归类为激动剂- 拮抗麻醉性镇痛药，作用强于吗啡。 然而，布托啡诺不受管制。 研究 文献报道主要进行如下 急性给药。 连续给药的效果 布托啡诺及其可能的后果（即耐受性/ 依赖性）尚未得到充分研究。 因此，这 该项目旨在提供一个动物模型来系统地 评估布托啡诺如何产生药理反应以及如何 布托啡诺诱导耐受/依赖于持续 行政。 目前现有的证据是最有力的 不同阿片受体参与的作用 布托啡诺。 以下具体目标旨在测试 根据可用的基本原理提出的假设。 四 提出了具体目标。 他们是： 目的 I. 急性布托啡诺作用的研究 给药方式及其与不同阿片类药物的关系 受体。 目标二。 使用布托啡诺的开发表征 连续脑室（ICV）输注模型 通过微型渗透泵释放布托啡诺。 目标三。 布托啡诺的开发表征 依赖性。 目标四。 拮抗特性的表征 吗啡依赖动物中的布托啡诺。 拟议的系统研究应（1）揭示机制 布托啡醇的作用，(2) 提高人们对滥用的认识 布托啡诺的责任，（3）建议采取某些预防措施 在使用布托啡诺期间考虑，（4）提供更多理由 用于治疗布托啡诺滥用，并且 (5) 确定 不同阿片受体在发展中的作用 对布托啡诺的耐受性和依赖性。