muopioid

The mu-opioid receptor, commonly referred to as MOR or the mu opioid receptor, is a seven-transmembrane G protein-coupled receptor that mediates many of the effects of endogenous and exogenous opioids. It is encoded by the OPRM1 gene and is a primary target for analgesia and other opioid-related effects.

Activation of MOR triggers Gi/Go protein signaling, leading to inhibition of adenylyl cyclase, reduced cyclic AMP levels, opening of potassium channels (GIRK), and closing of voltage-gated calcium channels. This results in hyperpolarization of neurons and decreased neurotransmitter release, contributing to analgesia and mood regulation. Receptor signaling can also involve downstream pathways that influence tolerance, dependence, and reward.

Mu-opioid receptors are widely distributed in the central nervous system and peripheral tissues. In the CNS, they are found in regions involved in pain processing and reward, including the dorsal horn of the spinal cord, periaqueductal gray, thalamus, cortex, nucleus accumbens, amygdala, and brainstem. Peripheral MORs are present on nociceptive neurons and in the gastrointestinal tract, where they affect pain signaling and motility.

Ligands for MOR include endogenous peptides such as beta-endorphin and enkephalins, and exogenous drugs including morphine, heroin, fentanyl, codeine, oxycodone, methadone, and buprenorphine. Pharmacological activation produces analgesia, euphoria, miosis, sedation, and suppression of cough, but also adverse effects such as respiratory depression, constipation, sedation, and potential for tolerance, dependence, and withdrawal.

Genetic variation in the OPRM1 gene (notably the A118G polymorphism) can influence individual responses to opioids, affecting analgesic efficacy and addiction risk in complex, context-dependent ways. Ongoing research explores receptor subtypes, signaling bias, and interactions with other opioid receptors to understand MOR function and improve therapeutic strategies.