The involvement of the μ-opioid receptor in gastrointestinal pathophysiology:: Therapeutic opportunities for antagonism at this receptor

被引：50

作者：

DeHaven-Hudkins, Diane L. ^{[1
]}

DeHaven, Robert N. ^{[1
]}

Little, Patrick J. ^{[1
]}

Techner, Lee M. ^{[1
]}

机构：

[1] Adolor Corp, Exton, PA 19341 USA

来源：

PHARMACOLOGY & THERAPEUTICS | 2008年 / 117卷 / 01期

关键词：

alvimopan; constipation; Ilens; gastrointestinal; methylnaltrexone; opioid-induced bowel dysfunction;

D O I：

10.1016/j.pharmthera.2007.09.007

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The localization of opioid receptors and their endogenous peptide ligands within the gastrointestinal (GI) tract and their role in the coordination of propulsion and secretion underscores the importance of opioid receptors in the maintenance of GI homeostasis. The peripherally acting mu-opioid receptor antagonists alvimopan and methylnaltrexone (MNTX) are currently under investigation as therapeutic agents to treat the deleterious GI side effects associated with opioid administration. These compounds have demonstrated efficacy in numerous animal models of GI function, and clinical studies have revealed their efficacy in the treatment of postoperative ileus (POI) and opioid-induced bowel dysfunction. Preservation of opioid-mediated analgesia has been demonstrated for these compounds in both the preclinical and clinical settings. Future studies exploring the benefits of selective antagonism of the peripheral g-opioid receptor in the treatment of other GI conditions may open new therapeutic opportunities for alvimopan and MNTX. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：162 / 187

页数：26

共 128 条

[1]

ALLAN L, 2001, BRIT MED J, V322, P1

[2]

AMIN HM, 1994, ANESTH ANALG, V78, P701

[3] INTERACTION OF THE OPIATE ANTAGONIST, NALTREXONE METHYL-BROMIDE, WITH THE ACETYLCHOLINE-RECEPTOR SYSTEM OF THE MOTOR ENDPLATE [J].