Mu, delta, and kappa opioid receptor (MOR, DOR, KOR)

Mu, delta, and kappa opioid receptors are three main subtypes of opioid receptors that belong to the G protein-coupled receptor (GPCR) superfamily. They are activated by endogenous opioid peptides (such as beta-endorphin for mu, enkephalins for delta, and dynorphins for kappa) as well as exogenous opioids (e.g., morphine, fentanyl, buprenorphine). Upon activation, these receptors primarily couple to inhibitory Gi/o proteins, leading to decreased neuronal excitability and reduced neurotransmitter release. The mu opioid receptor (MOR) is responsible for most clinical opioid effects, including analgesia, euphoria, respiratory depression, and dependence, and is the main target of opioid pain therapeutics and antagonists. The delta (DOR) and kappa (KOR) receptors contribute to pain modulation and have roles in mood regulation, addiction, and other physiological processes. The opioid receptors are distributed throughout the central and peripheral nervous system, mediating pain perception, reward pathways, mood, and autonomic functions. They are therapeutic targets for analgesia, addiction management, and are being explored for safer biased signaling agents to reduce side effects such as addiction, respiratory depression, and dysphoria[1][2][4][5][6][7].

Other names

Mu opioid receptor (MOR)Delta opioid receptor (DOR)Kappa opioid receptor (KOR)OPRM1 (gene for MOR)OPRD1 (gene for DOR)OPRK1 (gene for KOR)opioid receptors

Agonists activate Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP, leading to membrane hyperpolarization and inhibition of neurotransmitter release (analgesia, euphoria)[2][6]. Antagonists competitively block endogenous and exogenous opioid binding, reversing opioid effects (e.g., respiratory depression)[2][6]. Biased agonists preferentially activate G-protein over β-arrestin pathways for potentially improved safety/efficacy profiles[4].