Delta opioid receptor and Kappa opioid receptor (DOR and KOR)

The delta opioid receptor (DOR) and kappa opioid receptor (KOR) are two distinct members of the opioid receptor family of G protein-coupled receptors (GPCRs), primarily found in the nervous system. DOR is encoded by the OPRD1 gene, and KOR by the OPRK1 gene. Both receptors are activated by endogenous opioid peptides (enkephalins for DOR, dynorphins for KOR) and can also be targeted by synthetic agonists and antagonists[4][5][6]. DOR is most prominently involved in pain control, particularly under inflammatory conditions, and may also modulate mood and anxiety; it is a focus for non-addictive pain therapies[1][3]. KORs participate in pain modulation as well but their activation typically leads to dysphoria rather than euphoria and is less likely to produce abuse. Both have therapeutic potential in pain, mood disorders, and addiction, but drug development is limited by adverse effects and challenges in achieving selective, effective modulation[1][3][7].

Other names

DOR (Delta opioid receptor)KOR (Kappa opioid receptor)Delta-opioid receptor (also written as Delta receptor)Kappa-opioid receptor (also written as Kappa receptor)OPRD1 (gene symbol for Delta opioid receptor)OPRK1 (gene symbol for Kappa opioid receptor)

Agonism (activation) at the delta or kappa opioid receptor reduces neurotransmission by coupling to Gi/o proteins, inhibiting adenylate cyclase, reducing cAMP levels, hyperpolarizing neurons via increased potassium conductance, and inhibiting calcium channel opening, resulting in decreased neuronal excitability and pain transmission[3][4][5]. Antagonism (blockade) at these receptors prevents endogenous and exogenous opioid effects[4][6].