Nociceptin receptor (NOP)

The nociceptin receptor (NOP), encoded by the OPRL1 gene, is a G protein-coupled receptor that belongs to the opioid receptor family but is functionally and pharmacologically distinct from the classical μ, κ, and δ opioid receptors[1][2][4]. Its endogenous ligand is the neuropeptide nociceptin (or orphanin FQ), and upon ligand binding, NOP couples to inhibitory G proteins, modulating cyclic AMP production, potassium and calcium channel activity, and triggering diverse downstream signaling cascades[2][4]. NOP is involved in central nervous system regulation of pain perception, stress and anxiety, learning, memory, and reward, as well as peripheral processes such as immune regulation and cardiovascular function[1][2][4]. NOP agonists are being investigated as non-addictive analgesics with a more favorable side effect profile than classical opioids, while antagonists have therapeutic potential in mood disorders and neurodegenerative diseases[4]. Genetic and epigenetic modifications in OPRL1 have been linked to substance use vulnerabilities and psychiatric phenotypes[1].

Other names

Nociceptin/orphanin FQ receptorOPRL1OORORL1KOR-3NOCIRNOPrPNOCRKappa-type 3 opioid receptorOrphanin FQ receptorLC132 receptor-likekappa3-related opioid receptornociceptin/orphanin FQ receptoropiate receptor-like 1

NOP agonists: activation of G protein-coupled signaling, inhibition of adenylate cyclase, inhibition of calcium channel activity, activation of potassium channels; mediate antinociceptive (analgesic) and anti-reward effects NOP antagonists: block NOP-mediated signaling, may potentiate classical opioid receptor–mediated analgesia