Nociceptin/Orphanin FQ

Nociceptin/orphanin FQ (N/OFQ; FGGFTGARKSARKLANQ) was identified as the endogenous ligand of a previously orphan GPCR now referred to as N/OFQ peptide (NOP) receptor. The peptide and its receptor are widely distributed in the nervous system where via inhibitory mechanisms they modulate several different biological functions including pain, stress and anxiety, locomotor activity, emotional responses, feeding, learning and memory, reward, and addiction. N/OFQ is also able to modulate peripheral functions of the cardiovascular, respiratory, intestinal, genitourinary, and immune systems. The pleiotropic actions of N/OFQ suggest NOP-selective ligands as potential therapeutics for a variety of different pathological conditions. In particular, based on preclinical evidence the following indications seem to be promising: depression and Parkinson’s disease for NOP antagonists and anxiety and pain (after spinal administration) for NOP agonists. Finally clinical studies show that intravesical instillation of N/OFQ elicits beneficial effects in patients suffering from urinary incontinence resulting from an overactive bladder