Abstract
The idea of selectively targeting nociceptive transmission at the level of the peripheral nervous system is attractive from multiple perspectives, particularly the potential lack of non-specific (non-targeted) CNS side effects. Out of the multiple TRP channels involved in nociception, TRPV1 is a strong candidate based on its biophysical conductance properties and its expression in inflammation-sensitive dorsal root ganglion neurons and their axons and central and peripheral nerve terminals. While TRPV1 antagonists have undergone extensive medicinal chemical and pharmacological investigation, for TRPV1 agonists nature has provided an optimized compound in RTX. RTX is not suitable for systemic administration, but it is highly adaptable to a variety of pain problems when used by local administration. This can include routes as diverse as subcutaneous, intraganglionic or intrathecal (CSF space around the spinal cord). The present review focuses on the molecular and preclinical animal experiments that form the underpinnings of our clinical trial of intrathecal RTX for pain in advanced cancer. As such this represents a new approach to pain control that emerges from a long line of research on capsaicin and other vanilloids, their physiological actions, and the molecular biology of the capsaicin receptor TRPV1.
Keywords: Analgesia, hyperalgesia, cancer pain, osteosarcoma, canine, capsaicin, intrathecal, cerebrospinal fluid, spinal cord, dorsal root ganglion, proprioceptor, C-fiber, A-delta fiber, vanilloid receptor, calcium cytotoxicity, ion channel
Current Topics in Medicinal Chemistry
Title: The Vanilloid Agonist Resiniferatoxin for Interventional-Based Pain Control
Volume: 11 Issue: 17
Author(s): Michael J. Iadarola and Andrew J. Mannes
Affiliation:
Keywords: Analgesia, hyperalgesia, cancer pain, osteosarcoma, canine, capsaicin, intrathecal, cerebrospinal fluid, spinal cord, dorsal root ganglion, proprioceptor, C-fiber, A-delta fiber, vanilloid receptor, calcium cytotoxicity, ion channel
Abstract: The idea of selectively targeting nociceptive transmission at the level of the peripheral nervous system is attractive from multiple perspectives, particularly the potential lack of non-specific (non-targeted) CNS side effects. Out of the multiple TRP channels involved in nociception, TRPV1 is a strong candidate based on its biophysical conductance properties and its expression in inflammation-sensitive dorsal root ganglion neurons and their axons and central and peripheral nerve terminals. While TRPV1 antagonists have undergone extensive medicinal chemical and pharmacological investigation, for TRPV1 agonists nature has provided an optimized compound in RTX. RTX is not suitable for systemic administration, but it is highly adaptable to a variety of pain problems when used by local administration. This can include routes as diverse as subcutaneous, intraganglionic or intrathecal (CSF space around the spinal cord). The present review focuses on the molecular and preclinical animal experiments that form the underpinnings of our clinical trial of intrathecal RTX for pain in advanced cancer. As such this represents a new approach to pain control that emerges from a long line of research on capsaicin and other vanilloids, their physiological actions, and the molecular biology of the capsaicin receptor TRPV1.
Export Options
About this article
Cite this article as:
J. Iadarola Michael and J. Mannes Andrew, The Vanilloid Agonist Resiniferatoxin for Interventional-Based Pain Control, Current Topics in Medicinal Chemistry 2011; 11 (17) . https://dx.doi.org/10.2174/156802611796904942
DOI https://dx.doi.org/10.2174/156802611796904942 |
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
-
Therapeutic Drugs in Bone Loss-Associated Disorders: Clinical Outcomes and Challenges
Current Drug Targets MicroRNAs in Esophageal Adenocarcinoma: Functional Significance and Potential for the Development of New Molecular Disease Markers
Current Pharmaceutical Design The ‘Other’ Telomerase Inhibitors: Non-G-Quadruplex Interactive Agent, Non-Antisense, Non-Reverse Transcriptase Telomerase Inhibitors
Current Medicinal Chemistry - Anti-Cancer Agents Transition Metal-Based Prodrugs for Anticancer Drug Delivery
Current Medicinal Chemistry Chagas Disease Chemotherapy: What Do We Know So Far?
Current Pharmaceutical Design CXCR4 Inhibitors: Tumor Vasculature and Therapeutic Challenges
Recent Patents on Anti-Cancer Drug Discovery Bone-Targeted Doxorubicin-Loaded Nanoparticles as a Tool for the Treatment of Skeletal Metastases
Current Cancer Drug Targets Cellular Sensitivity to β-Diketonato Complexes of Ruthenium(III), Chromium(III) and Rhodium(III)
Medicinal Chemistry Rheumatoid Nodules and Lung
Current Respiratory Medicine Reviews Effect of Intestinal Flora Clearance on Liver Proteomics in Mice
Current Proteomics MICA Molecules in Disease and Transplantation, a Double-Edged Sword?
Current Immunology Reviews (Discontinued) Recent Advances in Thymidine Kinase 2 (TK2) Inhibitors and New Perspectives for Potential Applications
Current Pharmaceutical Design Anti-Angiogenic Therapies for Children with Cancer
Current Cancer Drug Targets Emerging Features in the Regulation of MMP-9 Gene Expression for the Development of Novel Molecular Targets and Therapeutic Strategies
Current Drug Targets - Inflammation & Allergy High-Content Analysis of Kinase Activity in Cells
Combinatorial Chemistry & High Throughput Screening Melatonin, A Natural Programmed Cell Death Inducer in Cancer
Current Medicinal Chemistry CYP24A1 as a Potential Target for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry RGD Peptide–mediated Molecular Imaging for Targeting Integrin Alpha(v) Beta(3) in Tumors: A Review
Current Medical Imaging Mesenchymal Stem Cells and Their Cell Surface Receptors
Current Rheumatology Reviews Signal Transduction and Photodynamic Therapy
Current Signal Transduction Therapy