deltaopioid

Delta opioid receptor, commonly referred to as the delta opioid receptor (DOR), is one of the three classical opioid receptors along with mu and kappa. It is a G protein-coupled receptor that primarily couples to Gi/Go proteins, leading to inhibition of adenylyl cyclase, reduced cyclic AMP, activation of GIRK channels, and decreased calcium influx. These effects collectively decrease neurotransmitter release and contribute to analgesic signaling in the nervous system.

Distribution and ligands. Delta receptors are found in both the central and peripheral nervous systems, with notable expression in limbic regions (such as the amygdala and hippocampus), the striatum, certain cortical areas, and dorsal horn neurons. Endogenous ligands are enkephalins, particularly met- and leu-enkephalin, which show affinity for delta receptors. Delta-selective peptides such as deltorphins and synthetic agonists (for example, DPDPE and SNC80) help characterize Delta receptor pharmacology. Antagonists include naltrindole, a selective delta antagonist.

Pharmacology and effects. Activation of delta receptors produces analgesia, often contributing to anti-nociceptive effects in spinal and supraspinal pathways. Delta agonists can modulate mu receptor signaling and may enhance or sustain mu-agonist analgesia, while potentially reducing tolerance development in some contexts. Other observed effects include mood-related changes, with some animal studies suggesting antidepressant- or anxiolytic-like effects. Side effects can include gastrointestinal disturbances and, at high doses in animal studies, convulsions or seizure-like activity, indicating a safety concern that has limited clinical translation. Tolerance and dependence have been reported in animal models, though the profile differs from mu agonists.

Clinical status and research. There are no delta-selective opioid drugs approved for routine clinical use as of the latest reviews. Delta receptors remain a target of interest for developing analgesics with potentially different safety profiles and for exploring roles in mood and affective disorders. OPRD1 is the gene encoding the delta opioid receptor, contributing to research on genetics and receptor function.

---