The potential therapeutic value of nociceptin receptor agonists and antagonists

Nociceptin (noc), a neuropeptide also known as orphanin FQ, is the endogenous ligand of the G protein-coupled receptor (GPCR) ORL1 (Opioid Receptor-Like1). Noc (FGGFTGARKSARKLANQ) bears a structural resemblance to opioid peptides, notably dynorphin A, and is synthesised as a larger precursor polypeptide, prepro-nociceptin (pp-noc), which is widely distributed in the nervous system. Noc is primarily an inhibitory neuropeptide that acts on neurones to depress synaptic transmission, either presynaptically by inhibiting transmitter release or postsynaptically by decreasing neuronal excitability. The peptide has been variously shown to modulate nociception, locomotion, stress and anxiety, food intake, neuroendocrine secretion, learning and memory, and smooth musculature tone in the cardiovascular system and respiratory, gastrointestinal and urogenital tracts. Unlike opioids, the peptide appears to be free of abuse potential, and may indeed possess anti-opioid/anti-addictive properties. The broad spectrum of pharmacological effects of noc suggests multiple therapeutic applications for ORL1 receptor agonists and antagonists.