Methylnaltrexone Mechanisms of Action and Effects on Opioid

Opioid medications are used exten-sively as potent analgesics for treat-ing moderate to severe pain. Although opioids offer excellent pain relief, their use is associated with a number of ad-verse effects (ADEs) such as constipation, nausea, and vomiting. Conventional mea-sures for ameliorating opioid-induced ADEs are often insufficient. Thus, reduc-ing the severity of these ADEs is of ut-most importance for patients who require the benefits of opioid analgesics. Since opioids mediate their pain-relieving ef-fects and ADEs through the same classes of receptors (ie, µ, δ, κ), it has been chal-lenging to dissociate beneficial effects from detrimental ones. Naloxone, naltrex-one, and nalmephene are clinically pre-scribed opioid antagonists. These nonse-lective opioid antagonists have been studied as a means of antagonizing the undesirable peripheral effects of opioids. However, because these compounds also enter the central nervous system, they re-verse analgesia or cause opioid withdraw-al symptoms.1-4 In the last 3 decades, de-spite considerable progress in understand-ing the pharmacologic actions of opioids, few advances have been made in the management of these ADEs. This failure has led to a search for compounds that selectively block opioid receptors out-side of the central nervous system