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.
Keywords: Antagonists, cloning, opioid receptor, G-protein coupled receptor (GPCR), peptide, ligand, Inflammatory Pain
Current Topics in Medicinal Chemistry
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/156802608786264227 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Suicide in Parkinson’s Disease: A Systematic Review
CNS & Neurological Disorders - Drug Targets Lipid Raft Alterations in Aged-Associated Neuropathologies
Current Alzheimer Research Association of Prolyl Oligopeptidase with Conventional Neurotransmitters in the Brain
CNS & Neurological Disorders - Drug Targets Metabotropic Glutamate Receptors in Central Nervous System Diseases
Current Drug Targets The Neuronal Cytoskeleton as a Potential Therapeutical Target in Neurodegenerative Diseases and Schizophrenia
Current Drug Targets - CNS & Neurological Disorders Is Ecto-nucleoside Triphosphate Diphosphohydrolase (NTPDase)-based Therapy of Central Nervous System Disorders Possible?
Mini-Reviews in Medicinal Chemistry Properties and Therapeutic Potential of Transient Receptor Potential Channels with Putative Roles in Adversity: Focus on TRPC5, TRPM2 and TRPA1
Current Drug Targets Association Between Atrophy of the Caudate Nuclei, Global Brain Atrophy, Cerebral Small Vessel Disease and Mild Parkinsonian Signs in Neurologically and Cognitively Healthy Subjects Aged 45-84 Years: A Crosssectional Study
Current Alzheimer Research Pharmacological Neuroprotection in Stroke: Rationale, State-of-the-art and Future Directions
Current Neuropharmacology Neurotuberculosis: An Overview
Central Nervous System Agents in Medicinal Chemistry Secretoneurin: A New Player in Angiogenesis and Chemotaxis Linking Nerves, Blood Vessels and the Immune System
Current Protein & Peptide Science Are Anti-Angiogenic Drugs Useful in Neurodegenerative Disorders?
CNS & Neurological Disorders - Drug Targets Role of Infrared Spectroscopy and Imaging in Cancer Diagnosis
Current Medicinal Chemistry GCH1, BH4 and Pain
Current Pharmaceutical Biotechnology Neuronal Regulators and Vascular Dysfunction in Raynauds Phenomenon and Systemic Sclerosis
Current Vascular Pharmacology Imaging of Organ Metabolism in Obesity and Diabetes: Treatment Perspectives
Current Pharmaceutical Design Role of Nitric Oxide in Motor Control: Implications for Parkinsons Disease Pathophysiology and Treatment
Current Pharmaceutical Design The Impact of Nandrolone Decanoate on the Central Nervous System
Current Neuropharmacology “Speed” Warps Time: Methamphetamines Interactive Roles in Drug Abuse, Habit Formation, and the Biological Clocks of Circadian and Interval Timing
Current Drug Abuse Reviews The Evolution of Pharmacological Treatment for Parkinsons Disease
Recent Patents on CNS Drug Discovery (Discontinued)