Mechanisms of opioid receptor desensitisation in single neurons

单个神经元阿片受体脱敏机制

• 批准号: nhmrc : 211169
• 负责人: Prof Macdonald Christie
• 金额: $ 20.09万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/mechanisms-opioid-receptor-single-neurons/81828
• 关键词: Mechanisms; opioid; receptor; desensitisation; single

Opioid drugs including morphine and codeine are the most effective analgesics known but their utility is limited by problems of tolerance (which is the need for increasing doses of drug to achieve the same effect), physical dependence characterised by a debilitating withdrawal syndrome on cessation of use, and addiction or compulsive drug seeking and use. Better understanding of the mechanisms underlying these adverse processes could lead to the development of more acceptable pain relieving agents. This project will increase understanding of the initial molecular events occurring in nerve cells that are believed to underlie the development of tolerance and physical dependence on opioid drugs. These studies will focus on sensory nerve cells isolated and cultured from animals, which are one of the major targets of pain relieving drugs. Understanding of these processes will lead to development of better strategies to avoid development of tolerance and perhaps physical dependence. They will also identify on a molecular level the mechanisms that determine why one opioid drug may produce more tolerance than another. This knowledge may lead to the development of pain relieving drugs that do not so readily lose their effectiveness in the management of chronic pain.

包括吗啡和可待因在内的阿片类药物是已知最有效的镇痛药，但它们的效用受到耐受性问题（即需要增加药物剂量才能达到相同效果）、以停止使用后衰弱的戒断综合征为特征的身体依赖性以及成瘾或强迫性寻求和使用药物等问题的限制。更好地了解这些不良过程背后的机制可能会导致开发出更可接受的止痛剂。该项目将增进对神经细胞中发生的初始分子事件的了解，这些事件被认为是对阿片类药物产生耐受性和身体依赖性的基础。这些研究将重点关注从动物中分离和培养的感觉神经细胞，这是止痛药物的主要目标之一。了解这些过程将有助于制定更好的策略，以避免产生耐受性和身体依赖性。他们还将在分子水平上确定决定为什么一种阿片类药物比另一种阿片类药物产生更高耐受性的机制。这些知识可能会导致止痛药物的开发，这些药物在治疗慢性疼痛方面不会轻易失去其有效性。