Orphanin Analogues

Orphanin FQ (OFQ or nociceptin) is an endogenously produced peptide agonist of the Orphanin receptor (ORL1 or OP₄).  Outside of the central nervous system, both the peptide and receptor are expressed in several peripheral organs including the intestine.  In the intestine, Orphanin FQ exerts a concentration-dependent contraction of the colonic smooth muscle.  Peripheral administration of the peptide in animal models was shown to accelerate transit rate in the large intestine, an action opposite to that induced by opioids.  Clinically, opioid medication use has been associated with severe gastrointestinal side-effects, including constipation, preventing their optimal use in pain control.

Our primary research objective is to identify Orphanin Agonists for the treatment of gastrointestinal complications such as Post-operative Ileus, ipioid-induced bowel dysfunction (OBD) and severe constipation.  Our secondary research objective is to identify Orphanin Antagonists to aid in the relief of diarrhea and Irritable Bowel Syndrome (IBS).

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