Mu opioid receptor antagonists: Recent developments

作者：Goodman Allan J^*; Le Bourdonnec Bertrand; Dolle Roland E

来源：ChemMedChem, 2007, 2(11): 1552-1570.

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 ore still used as a first line therapy in the treatment of moderate to severe pain. However, despite the clear benefits of mu ogonists in pain management, severe side effects such as dependence and respiratory depression are associated with use of these drugs. To dote, there ore 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 hove 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 ore 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 lost ten years.

• 出版日期2007-11