The ORL-1 Receptor System: Are There Opportunities for Antagonists in Pain Therapy?

Title: The ORL-1 Receptor System: Are There Opportunities for Antagonists in Pain Therapy?

Volume: 8 Issue: 16

Author(s): Beatriz Fioravanti and Todd W. Vanderah

Affiliation:

Keywords: Antagonists, cloning, opioid receptor, G-protein coupled receptor (GPCR), peptide, ligand, Inflammatory Pain

Abstract: Following the cloning of the classical opioid receptors (μ, δ and κ), the opioid receptor like-1 (ORL-1) was identified as a G-protein coupled receptor (GPCR) with 65% structure homology to the other members of the opioid family. Its endogenous ligand nociception/orphanin FQ (N/OFQ) was discovered shortly thereafter, becoming the subject of investigation in numerous studies. Since activation of the ORL-1 receptor by N/OFQ leads to Gαi-coupling and signal transduction similar to that of opioid receptors, N/OFQ was thought to have a role in pain modulation, similar to that of the endogenous opioids. Surprisingly, studies characterizing N/OFQs effects on pain transmission yielded conflicting results, attributing to N/OFQ both pronociceptive and antinociceptive actions, depending on doses and routes of administration as well as species and sex of the subjects. With the development of selective and potent ORL-1 antagonists, many scientists believed these contradicting actions would be elucidated. Here we review the recent literature reporting the use of novel ORL-1 antagonists, both peptide and non-peptide, in different models of pain and discuss their use as research tools or potential drug candidates.

Cite this article as:

Fioravanti Beatriz and Vanderah W. Todd, The ORL-1 Receptor System: Are There Opportunities for Antagonists in Pain Therapy?, Current Topics in Medicinal Chemistry 2008; 8 (16) . https://dx.doi.org/10.2174/156802608786264227