Nociceptin

Pain / Anxiety / Addiction

Also known as: Orphanin FQ, N/OFQ, Nociceptin/Orphanin FQ, PNOC

Opioid-Related PeptidesResearch phase: Endogenous peptide (NOP-targeting drugs in clinical trials)Regulatory: Endogenous peptide. NOP receptor agonists/antagonists are in clinical trials for pain and addiction. Cebranopadol is a MOR/NOP agonist in Phase 3.

Mechanism

Nociceptin (also called orphanin FQ) is a 17-amino-acid peptide that resembles opioids structurally but acts on its own unique receptor (NOP/ORL-1). Unlike classical opioids, it does not produce euphoria or respiratory depression. Its effects are complex and context-dependent: it can be both pro-pain and anti-pain depending on the brain region. It is involved in anxiety, stress responses, and addiction, making the NOP receptor an attractive drug target.

Technical detail

Nociceptin/Orphanin FQ (N/OFQ, 17aa) is derived from prepronociceptin (PNOC) and is the endogenous ligand of the NOP receptor (ORL-1), a Gi/Go-coupled GPCR structurally related to classical opioid receptors but pharmacologically distinct. NOP activation inhibits adenylyl cyclase, activates GIRK channels, and inhibits N-type Ca2+ channels. At supraspinal levels (PAG), nociceptin is anti-opioid and hyperalgesic (opposing mu-opioid analgesia). At spinal levels, it is analgesic. NOP activation reduces dopamine release in the reward circuit without producing reinforcement. NOP agonists (cebranopadol) and bifunctional MOR/NOP agonists are in clinical trials for pain and addiction.

Build a personalized protocol with Nociceptin →