What is the mechanism of action for Naloxegol (Movantik), Methylnaltrexone (Relistor), and Naldemedine (Symproic)?

The mechanism of action for Naloxegol (Movantik), Methylnaltrexone (Relistor), and Naldemedine (Symproic) is that they function as mu opioid receptor antagonists. These medications are specifically designed to counteract the effects of opioids in the gastrointestinal tract, thereby preventing or alleviating opioid-induced constipation (OIC) without affecting analgesia provided by opioids in the central nervous system.

By antagonizing the mu opioid receptors in the gut, these drugs allow for normal bowel function and movement, as the mu opioid receptors when activated by opioids can slow down gut motility and increase transit time, leading to constipation. Importantly, these agents are designed with a structure that limits their ability to cross the blood-brain barrier, ensuring they do not interfere with the pain-relieving effects of opioids while achieving their intended purpose of alleviating constipation. This selective action is crucial for patients who require opioid therapy for pain management but struggle with gastrointestinal side effects.