Abstract
In primary sensory neurons, the capsaicin receptor TRPV1 functions as a molecular integrator for a broad range of seemingly unrelated chemical and physical noxious stimuli, including heat and altered pH. Indeed, TRPV1 is thought to be a major transducer of the thermal hyperalgesia that follows inflammation and tissue injury as this response is impaired in TRPV1-deficient mice. Following the molecular cloning of TRPV1 in 1997, over a dozen companies embarked on efforts to find clinically useful TRPV1 antagonists, but side-effects and limited efficacy have thus far prevented any compounds from progressing beyond phase II. This has rekindled interest in desensitization of nociceptive neurons to TRPV1 agonists (e.g. capsaicin and its ultrapotent analog resiniferatoxin) as an alternative pharmacological approach to block pain in the periphery where it is generated. The clinical value of capsaicin is, however, limited by its unfavorable irritancy to desensitization ratio. In animal experiments, resiniferatoxin treatment is a powerful approach to achieve longlasting analgesia. In patients with overactive bladder, intravesical resiniferatoxin improves bladder function (or even restores continence) without significant irritancy and/or toxicity. In this review, we argue that resiniferatoxin is an attractive alternative to capsaicin in that it achieves lasting desensitization without the side effects that complicate capsaicin therapy.
Keywords: Capsaicin, resiniferatoxin, the capsaicin (vanilloid) receptor TRPV1, neuropathic pain, inflammatory thermal hyperalgesia, overactive bladder, primary sensory neurons, capsaicin receptor TRPV1, chemical and physical noxious stimuli, thermal hyperalgesia, inflammation, tissue injury, TRPV1-deficient mice, molecular cloning of TRPV1, efficacy
Current Topics in Medicinal Chemistry
Title: Therapeutic Targeting of TRPV1 by Resiniferatoxin, from Preclinical Studies to Clinical Trials
Volume: 11 Issue: 17
Author(s): Igor Kissin and Arpad Szallasi
Affiliation:
Keywords: Capsaicin, resiniferatoxin, the capsaicin (vanilloid) receptor TRPV1, neuropathic pain, inflammatory thermal hyperalgesia, overactive bladder, primary sensory neurons, capsaicin receptor TRPV1, chemical and physical noxious stimuli, thermal hyperalgesia, inflammation, tissue injury, TRPV1-deficient mice, molecular cloning of TRPV1, efficacy
Abstract: In primary sensory neurons, the capsaicin receptor TRPV1 functions as a molecular integrator for a broad range of seemingly unrelated chemical and physical noxious stimuli, including heat and altered pH. Indeed, TRPV1 is thought to be a major transducer of the thermal hyperalgesia that follows inflammation and tissue injury as this response is impaired in TRPV1-deficient mice. Following the molecular cloning of TRPV1 in 1997, over a dozen companies embarked on efforts to find clinically useful TRPV1 antagonists, but side-effects and limited efficacy have thus far prevented any compounds from progressing beyond phase II. This has rekindled interest in desensitization of nociceptive neurons to TRPV1 agonists (e.g. capsaicin and its ultrapotent analog resiniferatoxin) as an alternative pharmacological approach to block pain in the periphery where it is generated. The clinical value of capsaicin is, however, limited by its unfavorable irritancy to desensitization ratio. In animal experiments, resiniferatoxin treatment is a powerful approach to achieve longlasting analgesia. In patients with overactive bladder, intravesical resiniferatoxin improves bladder function (or even restores continence) without significant irritancy and/or toxicity. In this review, we argue that resiniferatoxin is an attractive alternative to capsaicin in that it achieves lasting desensitization without the side effects that complicate capsaicin therapy.
Export Options
About this article
Cite this article as:
Kissin Igor and Szallasi Arpad, Therapeutic Targeting of TRPV1 by Resiniferatoxin, from Preclinical Studies to Clinical Trials, Current Topics in Medicinal Chemistry 2011; 11 (17) . https://dx.doi.org/10.2174/156802611796904924
DOI https://dx.doi.org/10.2174/156802611796904924 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Hypertension and Concurrent Arrhythmias
Current Pharmaceutical Design Twin-to-Twin Transfusion Syndrome: From Placental Anastomoses to Long-Term Neurodevelopmental Outcome
Current Pediatric Reviews Pyrrolo-isoxazole: A Key Molecule with Diverse Biological Actions
Mini-Reviews in Medicinal Chemistry Vascular and Cellular Calcium in Normal and Hypertensive Pregnancy
Current Clinical Pharmacology Nebivolol: More Than a Highly Selective Beta Blocker
Recent Patents on Cardiovascular Drug Discovery The Effects of Newer Beta-Adrenoceptor Antagonists on Vascular Function in Cardiovascular Disease
Current Vascular Pharmacology Peptide Metabolism and the Control of Body Fluid Homeostasis
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Stress, Cardiovascular Diseases and Surgery-Induced Angiogenesis
Current Angiogenesis (Discontinued) Targeting the Noradrenergic System in Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis of Prazosin Trials
Current Drug Targets Importance of ABC Transporters in Drug Development
Current Pharmaceutical Design Increasing Sensitivity to Radiotherapy and Chemotherapy by Using Novel Biological Agents that Alter the Tumor Microenvironment
Current Molecular Medicine Anti-VEGF Strategies – from Antibodies to Tyrosine Kinase Inhibitors: Background and Clinical Development in Human Cancer
Current Pharmaceutical Design Angiotensin, The Hormone to be Blocked by Antithypertensive Drugs, and Perhaps Why They Dont Work
Current Vascular Pharmacology Is Combination Therapy of Atosiban and Nifedipine More Effective in Preterm Labor than Each Drug Alone? A Prospective Study
Current Women`s Health Reviews Targeting Nanoparticles as Drug Delivery Systems for Cancer Treatment
Current Nanoscience Phosphodiesterase Inhibition as a Therapeutic Target for Brain Ischemia
CNS & Neurological Disorders - Drug Targets Clinical Vignettes: Integrated Care of Cancer Patients by Oncologists and Cardiologists
Current Cardiology Reviews Pharmacological Potential of Exercise and RAS Vasoactive Peptides for Prevention of Diseases
Current Protein & Peptide Science Concise Review of the Rationale for Pulmonary Embolism Treatment and Endovascular Device Therapies
Current Cardiology Reviews The Treatment of Behavioral and Psychological Symptoms of Dementia: Weighing Benefits and Risks
Current Alzheimer Research