Nociceptin receptor (NOP) (NOP)

The nociceptin receptor (NOP), also known as the orphanin FQ receptor, is a G protein-coupled receptor (GPCR) that is structurally related to classical opioid receptors but possesses distinct pharmacological properties (UniProt: P41146). It is primarily activated by the endogenous neuropeptide nociceptin/orphanin FQ and is widely distributed throughout the central and peripheral nervous systems, particularly in regions associated with pain transmission, mood regulation, and reward circuitry (IUPHAR/BPS Guide to Pharmacology). The NOP receptor plays a dual role in pain modulation, acting as an anti-nociceptive agent in the spinal cord while sometimes exhibiting pro-nociceptive effects in the brain (PMID: 25832144). It is also heavily involved in the pathophysiology of anxiety, depression, and substance use disorders. Buprenorphine, a key therapeutic agent for opioid dependence and chronic pain, acts as a partial agonist at the NOP receptor, which is thought to contribute to its unique ceiling effect on respiratory depression and its efficacy in reducing drug-seeking behavior (StatPearls: Buprenorphine). Targeting the NOP receptor remains a significant area of interest for developing non-addictive analgesics and treatments for psychiatric conditions.

Other names

Orphanin FQ receptorORL1OPRL1Nociceptin/orphanin FQ peptide receptorKappa-type 3 opioid receptor

Buprenorphine acts as a partial agonist at the nociceptin receptor (NOP), while simultaneously acting as a partial agonist at the mu-opioid receptor (MOR) and an antagonist at the kappa-opioid (KOR) and delta-opioid (DOR) receptors (StatPearls: Buprenorphine; PMID: 25832144).