The ORL-1 receptor system: Are there opportunities for antagonists in pain therapy?

Beatriz Fioravanti, Todd W. Vanderah

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations


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 G i-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/OFQ's 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.

Original languageEnglish (US)
Pages (from-to)1442-1451
Number of pages10
JournalCurrent topics in medicinal chemistry
Issue number16
StatePublished - 2008

ASJC Scopus subject areas

  • Drug Discovery


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