Mu- and Delta-type opioid receptors (MOR; DOR)

The mu opioid receptor and delta opioid receptor are subtypes of the opioid receptor family, both belonging to the GPCR superfamily and characterized by seven-transmembrane domains[3][4]. Mu receptors predominantly mediate the analgesic and reward-related effects of opioids and are the main molecular targets for opioid pain medications and drugs of abuse[4][5][6]. Delta receptors also contribute to analgesia and modulate emotional responses but have distinct pharmacological and regulatory properties[3][7]. Both receptors are widely expressed in the central and peripheral nervous systems, and their activation modulates neuronal activity via Gi/Go protein signaling, leading to inhibition of adenylate cyclase and changes in ion channel activity[3][4][6][7]. Structural studies, including crystal and cryo-EM, have elucidated ligand binding mechanisms and facilitated the design of new agonists and antagonists, including those with "biased" signaling properties aimed at improving safety and efficacy[1][2][5]. While mu receptor agonists are highly effective analgesics, they are also prone to significant side effects (addiction, respiratory depression), motivating ongoing development of new therapeutics with improved safety profiles[3][5][6]. Delta receptor agonists represent promising non-addictive analgesics but are limited by lower efficacy and the risk of seizures in some cases[3][7]. Genetic variants in both receptors influence individual responses to drugs and are relevant for personalized medicine[6].

Other names

μ-opioid receptorMOROPRM1δ-opioid receptorDOROPRD1

Agonism: Activation of Gi/Go signaling pathway → inhibition of adenylyl cyclase → decreased cAMP → reduced neuronal excitability and neurotransmitter release\nBiased agonism: Preference for signaling via either G proteins or β-arrestin pathways, affecting efficacy and side effect profile\nAntagonism: Blockade of opioid receptor, reversing or preventing opioid effects