Delta-type opioid receptor (DOR) (DOR)

The Delta-type opioid receptor (DOR), encoded by the OPRD1 gene, is a G protein-coupled receptor (GPCR) that serves as a key modulator of pain, mood, and emotional states [UniProt P41143]. It is primarily expressed in the central nervous system, with high densities in the cerebral cortex, striatum, and the dorsal horn of the spinal cord, where it interacts with endogenous enkephalins to regulate neurotransmission [IUPHAR/BPS Guide to Pharmacology]. Unlike the mu-opioid receptor, DOR activation provides effective analgesia for chronic and inflammatory pain with a significantly lower risk of respiratory depression and constipation [PubMed PMID: 26433067]. Furthermore, DOR is a prominent target for treating neuropsychiatric conditions, as its agonists exhibit potent anxiolytic and antidepressant-like properties in various models [StatPearls]. Despite its therapeutic potential, the clinical advancement of DOR-targeted drugs has been hindered by safety concerns, most notably the pro-convulsant activity associated with certain agonist scaffolds [PubMed PMID: 26433067]. Current drug development efforts are focused on identifying biased ligands or selective modulators that retain analgesic and mood-enhancing benefits while minimizing seizure risk.

Other names

OPRD1Delta opioid receptorOPRDDOR-1Enkephalin receptor

Agonist binding triggers Gi/o protein coupling, which inhibits adenylyl cyclase activity, decreases cAMP levels, closes voltage-gated calcium channels, and opens G protein-activated inwardly rectifying potassium (GIRK) channels, resulting in neuronal hyperpolarization and reduced neurotransmitter release [UniProt P41143, IUPHAR/BPS Guide to Pharmacology].