Recently patented and promising ORL-1 ligands: where have we been and where are we going?

The interactions of nociceptin/orphanin FQ (N/OFQ) and the opioid receptor-like receptor 1 (nociceptin opioid peptide--NOP) have been implicated in a variety of systems including cardiovascular, respiratory, immune, and the central and peripheral nervous systems.

To elucidate the endogenous role of the N/OFQ-NOP system through the use of knockout and knockdown animal preparations, though most advances have been made using a host of synthetic agonists and antagonists. This review gives a brief history of the receptor-ligand discovery, the development of these agonists and antagonists within the last 10 years as published, and the therapeutic indications thereof focusing on pain.

The use of NOP ligands in pain has been controversial at best; however, there are indications that both agonists and antagonists have a place in the clinical setting for acute and chronic pain. NOP ligands have potential as novel therapeutics, interestingly, when incorporated into a rationally-designed multi-target agent.

The discovery of N/OFQ and NOP opened a new option for the treatment of pain with the potential for a decreased side effect profile. Numerous compounds have been designed to target this system, the most promising of which have mixed profiles.