Mu-type opioid receptor (MOR)

The Mu-type opioid receptor (MOR), encoded by the OPRM1 gene, is a G protein-coupled receptor that serves as the primary mediator for the effects of endogenous opioids and therapeutic opioid analgesics (UniProt: P35372). While MORs in the central nervous system are responsible for analgesia and sedation, those located in the peripheral nervous system, particularly within the myenteric and submucosal plexuses of the gastrointestinal tract, regulate bowel function (StatPearls: Opioid-Induced Constipation). Activation of peripheral MORs inhibits the release of excitatory neurotransmitters like acetylcholine, leading to decreased intestinal motility and increased fluid absorption, which frequently results in opioid-induced constipation (OIC) (PubMed: PMC4590096). To address this, peripherally acting mu-opioid receptor antagonists (PAMORAs) such as methylnaltrexone and naloxegol have been developed to block these receptors in the gut without crossing the blood-brain barrier, thus maintaining central pain relief (NIH: LiverTox). Conversely, peripheral MOR agonists like loperamide are used to treat diarrhea by slowing gastrointestinal transit (PubChem: CID 3955). Beyond the gut, peripheral MORs are also found on primary afferent neurons where they can modulate inflammatory pain (PubMed: PMC3070647). This target is central to managing the side effects of chronic opioid therapy while maintaining its therapeutic efficacy.

Other names

OPRM1Mu opioid receptorMOPOpioid receptor mu 1Peripheral mu opioid receptor

Peripherally acting mu-opioid receptor antagonists (PAMORAs) selectively inhibit mu-opioid receptors in the gastrointestinal tract to restore motility, while peripheral agonists activate these receptors to reduce intestinal secretion and transit speed.