首页> 外文期刊>Life sciences >Basal opioid receptor activity, neutral antagonists, and therapeutic opportunities.
【24h】

Basal opioid receptor activity, neutral antagonists, and therapeutic opportunities.

机译:基础阿片受体活性,中性拮抗剂和治疗机会。

获取原文
获取原文并翻译 | 示例
           

摘要

The mu opioid receptor (MOR, OPRM)--the principal receptor involved in narcotic addiction--has been shown to display basal (spontaneous, constitutive) signaling activity. Interaction with other signaling proteins, such as calmodulin, regulates basal MOR activity. Providing a mechanism for long-lasting regulation, basal MOR activity potentially plays a key role in addiction, in combination with gene regulation and synaptic remodeling. Recent results support a link to physical dependence--one of the main manifestations of addiction to drugs of abuse. The prototypical opioid antagonists, naloxone and naltrexone, were shown to act as inverse agonists in the morphine-dependent state (i.e., they suppress basal MOR signaling) and thereby appear to elicit or contribute to precipitated withdrawal. This affords the opportunity to explore therapeutic applications for neutral antagonists (blocking agonists at MOR without affecting basal activity) with reduced adverse effects. Neutral antagonists are promising drugcandidates in the treatment of addiction and overdose, and of peripheral adverse effects of narcotic analgesics.
机译:mu阿片类药物受体(MOR,OPRM)是参与麻醉成瘾的主要受体,已显示出基础(自发,组成型)信号传导活性。与其他信号蛋白(例如钙调蛋白)的相互作用可调节基础MOR活性。基本的MOR活动为成瘾提供了持久的调节机制,与基因调节和突触重塑相结合,可能在成瘾中起关键作用。最近的结果支持与身体依赖性的联系,后者是滥用药物成瘾的主要表现之一。典型的阿片类药物拮抗剂纳洛酮和纳曲酮在吗啡依赖性状态下起反向激动剂的作用(即,它们抑制基础MOR信号传导),从而似乎引起或促成戒断。这提供了探索副作用减少的中性拮抗剂(在MOR处阻断激动剂而不影响基础活性)的治疗应用的机会。中性拮抗剂在治疗成瘾和药物过量以及麻醉性镇痛药的周围不良反应方面是有希望的候选药物。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号