Development and use of methylnaltrexone, a peripherally acting opioid antagonist, to treat side effects related to opioid use

Abstract

Opioid medications are used extensively as potent analgesics for treating moderate to severe pain. Although opioids offer reliable pain relief, their use is associated with a number of adverse effects, especially constipation. Conventional measures for ameliorating opioid-induced adverse effects are often insufficient. Thus, reducing the severity of these adverse effects is of utmost importance for patients who require the benefits of opioid analgesics. Since opioids mediate pain-relieving and adverse effects through the same classes of receptors, i.e., mu, delta, and kappa, it has been challenging to dissociate beneficial effects from detrimental ones. Methylnaltrexone is the first peripherally acting opioid receptor antagonist to receive FDA approval. This compound offers the therapeutic potential to block or reverse the undesired side effects of opioids that are mediated by receptors located in the periphery (e.g., in the gastrointestinal tract), without affecting analgesia or precipitating opioid withdrawal symptoms, which are mediated predominantly by receptors in the central nervous system. This review provides a history of the development of methylnaltrexone, discusses studies that relate to opioid bowel dysfunction, and explores other uses of this compound. Drug Dev Res 70 : 403-416, 2009.