Mu Opioid Receptor Antagonists: Recent Developments

• Published in: ChemMedChem Vol. 2; no. 11; pp. 1552 - 1570
• Main Authors: Goodman, Allan J., Le Bourdonnec, Bertrand, Dolle, Roland E.
• Format: Journal Article
• Language: English; German
• Published: Weinheim WILEY-VCH Verlag 12.11.2007; WILEY‐VCH Verlag
• Subjects: Humans; mu agonists; mu antagonists; Narcotic Antagonists - adverse effects; Narcotic Antagonists - chemistry; Narcotic Antagonists - pharmacology; opioids; Pain - physiopathology; receptors; Receptors, Opioid, mu - antagonists & inhibitors; Receptors, Opioid, mu - physiology; Structure-Activity Relationship
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.200700143

For thousands of years mu opioid agonists such as morphine have been utilized for their analgesic properties. Today, morphine and related compounds are still used as a first line therapy in the treatment of moderate to severe pain. However, despite the clear benefits of mu agonists in pain management, severe side effects such as dependence and respiratory depression are associated with use of these drugs. To date, there are only two approved mu opioid antagonists for use in the treatment of these adverse effects, that is, naloxone and naltrexone. However, many other clinical and therapeutic areas have been linked to mu opioid receptor antagonism. These include treatment of opioid induced pruritis of the skin, obesity, and Parkinson‐induced tardive dyskinesia. Currently there are two compounds, N‐methylnaltrexone and alvimopan, under FDA review as possible treatments for opioid induced bowel dysfunction and postoperative ileus. These compounds are of special interest as they are peripherally restricted. This attribute enables treatment of peripheral side effects induced by opioid agonists without reversal of the centrally mediated analgesia of the agonist. In this article we discuss the structural classes of mu opioid antagonists, their potential clinical applications, and review the relevant patents of the last ten years. Modifying morphine. There has been an extensive amount of research performed during the last ten years on mu opioid receptor antagonists. The positive clinical data generated with N‐methylnaltrexone and alvimopan has greatly contributed to a renewed interest in this field. In this article we review various chemical classes of mu opioid receptor antagonists and the clinical applications for this class of agents.