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

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

Journal Name: Current Topics in Medicinal Chemistry

Volume 8 , Issue 16 , 2008

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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.

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

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Article Details

Year: 2008
Page: [1442 - 1451]
Pages: 10
DOI: 10.2174/156802608786264227
Price: $58

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