Abstract
This review gives a brief overview of the expression patterns, molecular pharmacology and physiological roles of the vanilloid receptor 1 (VR1). Particular emphasis is given to the therapeutic utility of VR1 modulators. Small molecule agonists of VR1, including capsaicin and RTX, are currently utilized for a number of clinical syndromes, including intractable neuropathic pain, spinal detrusor hyperreflexia, and bladder hypersensitivity; however, antagonists of VR1 have yet to reach the clinic. While the classic VR1 antagonist, capsazepine has proven a useful tool for unraveling the molecular pharmacology of VR1, in vivo studies with this compound have had limited success due to poor pharmacokinetic properties and species selectivity issues. With the cloning of VR1 in 1997, the pharmaceutical community has been provided a molecular target for high throughput screening and small molecule lead discovery and optimization. As a result, resurgence in the interest of VR1 antagonists has given way to many new pharmacological agents that may provide better tools to probe VR1 physiology, and ultimately yield promising therapeutic agents.
Keywords: vr1, capsaicin, resiniferatoxin, antagonist, hyperalgesia, pain, capsazepine, inflammation
Current Medicinal Chemistry
Title: Current Perspectives on the Therapeutic Utility of VR1 Antagonists
Volume: 11 Issue: 24
Author(s): K. J. Valenzano and Q. Sun
Affiliation:
Keywords: vr1, capsaicin, resiniferatoxin, antagonist, hyperalgesia, pain, capsazepine, inflammation
Abstract: This review gives a brief overview of the expression patterns, molecular pharmacology and physiological roles of the vanilloid receptor 1 (VR1). Particular emphasis is given to the therapeutic utility of VR1 modulators. Small molecule agonists of VR1, including capsaicin and RTX, are currently utilized for a number of clinical syndromes, including intractable neuropathic pain, spinal detrusor hyperreflexia, and bladder hypersensitivity; however, antagonists of VR1 have yet to reach the clinic. While the classic VR1 antagonist, capsazepine has proven a useful tool for unraveling the molecular pharmacology of VR1, in vivo studies with this compound have had limited success due to poor pharmacokinetic properties and species selectivity issues. With the cloning of VR1 in 1997, the pharmaceutical community has been provided a molecular target for high throughput screening and small molecule lead discovery and optimization. As a result, resurgence in the interest of VR1 antagonists has given way to many new pharmacological agents that may provide better tools to probe VR1 physiology, and ultimately yield promising therapeutic agents.
Export Options
About this article
Cite this article as:
Valenzano J. K. and Sun Q., Current Perspectives on the Therapeutic Utility of VR1 Antagonists, Current Medicinal Chemistry 2004; 11 (24) . https://dx.doi.org/10.2174/0929867043363686
DOI https://dx.doi.org/10.2174/0929867043363686 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Nucleoside Inhibitors of Coronaviruses
Current Medicinal Chemistry Multiple Drug Resistance Associated with Function of ABC-Transporters in Diabetes Mellitus: Molecular Mechanism and Clinical Relevance
Infectious Disorders - Drug Targets Does Ceruloplasmin Defend Against Neurodegenerative Diseases?
Current Neuropharmacology PRAME/EZH2-Mediated Regulation of TRAIL: A New Target for Cancer Therapy
Current Molecular Medicine Acetaminophen Oxidation and Inflammatory Markers – A Review of Hepatic Molecular Mechanisms and Preclinical Studies
Current Drug Targets Effects of Exercise and Ferulic Acid on Alpha Synuclein and Neuroprotective Heat Shock Protein 70 in An Experimental Model of Parkinsonism Disease
CNS & Neurological Disorders - Drug Targets The p35 Family of Apoptosis Inhibitors
Current Genomics Behavioral Experimental Paradigms for the Evaluation of Drug’s Influence on Cognitive Functions: Interpretation of Associative, Spatial/Nonspatial and Working Memory
CNS & Neurological Disorders - Drug Targets Evaluation of the Antidiabetic Property of Capparis Ovata Desf. Var. Palaestina Zoh. Extracts Using In vivo and In vitro Approaches
Endocrine, Metabolic & Immune Disorders - Drug Targets New Approaches to Target the Androgen Receptor and STAT3 for Prostate Cancer Treatments
Mini-Reviews in Medicinal Chemistry Synthesis and Biological Activities of Organotin(IV) Complexes as Antitumoral and Antimicrobial Agents. A Review
Mini-Reviews in Medicinal Chemistry Nucleic Acid-based Molecular Treatment of Allergy
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Development and Validation of a UPLC–MS/MS Method for the Simultaneous Determination of Telmisartan and Metformine HCl in Human Plasma
Current Analytical Chemistry Chiral Kinase Inhibitors
Current Topics in Medicinal Chemistry Role of Sex Hormones in Regulating Innate Immune Protection against HIV in the Human Female Reproductive Tract
Current Immunology Reviews (Discontinued) An overview of ABC and SLC Drug Transporter Gene Regulation
Current Drug Metabolism Interferon-beta Inhibits Th17 Cell Differentiation in Patients with Multiple Sclerosis
Endocrine, Metabolic & Immune Disorders - Drug Targets Melatonin, A Natural Programmed Cell Death Inducer in Cancer
Current Medicinal Chemistry Bisphosphonates: Molecular Mechanisms of Action and Effects on Bone Cells, Monocytes and Macrophages
Current Pharmaceutical Design Structure, Function, and Pathogenesis of SHP2 in Developmental Disorders and Tumorigenesis
Current Cancer Drug Targets