Abstract
Ziconotide (PRIALT®) is a neuroactive peptide in the final stages of clinical development as a novel non-opioid treatment for severe chronic pain. It is the synthetic equivalent of ω-MVIIA, a component of the venom of the marine snail, Conus magus. The mechanism of action underlying ziconotides therapeutic profile derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels (NVSCCs). Direct blockade of N-VSCCs inhibits the activity of a subset of neurons, including pain-sensing primary nociceptors. This mechanism of action distinguishes ziconotide from all other analgesics, including opioid analgesics. In fact, ziconotide is potently anti-nociceptive in animal models of pain in which morphine exhibits poor anti-nociceptive activity. Moreover, in contrast to opiates, tolerance to ziconotide is not observed. Clinical studies of ziconotide in more than 2,000 patients reveal important correlations to ziconotides non-clinical pharmacology. For example, ziconotide provides significant pain relief to severe chronic pain sufferers who have failed to obtain relief from opiate therapy and no evidence of tolerance to ziconotide is seen in these patients. Contingent on regulatory approval, ziconotide will be the first in a new class of neurological drugs: the N-type calcium channel blockers, or NCCBs. Its novel mechanism of action as a non-opioid analgesic suggests ziconotide has the potential to play a valuable role in treatment regimens for severe chronic pain. If approved for clinical use, ziconotide will further validate the neuroactive venom peptides as a source of new and useful medicines.
Keywords: ziconotide, prialt, snx-111, n-type calcium channels, pain, analgesia, analgesic, conopeptide, conotoxin
Current Medicinal Chemistry
Title: Ziconotide: Neuronal Calcium Channel Blocker for Treating Severe Chronic Pain
Volume: 11 Issue: 23
Author(s): G. P. Miljanich
Affiliation:
Keywords: ziconotide, prialt, snx-111, n-type calcium channels, pain, analgesia, analgesic, conopeptide, conotoxin
Abstract: Ziconotide (PRIALT®) is a neuroactive peptide in the final stages of clinical development as a novel non-opioid treatment for severe chronic pain. It is the synthetic equivalent of ω-MVIIA, a component of the venom of the marine snail, Conus magus. The mechanism of action underlying ziconotides therapeutic profile derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels (NVSCCs). Direct blockade of N-VSCCs inhibits the activity of a subset of neurons, including pain-sensing primary nociceptors. This mechanism of action distinguishes ziconotide from all other analgesics, including opioid analgesics. In fact, ziconotide is potently anti-nociceptive in animal models of pain in which morphine exhibits poor anti-nociceptive activity. Moreover, in contrast to opiates, tolerance to ziconotide is not observed. Clinical studies of ziconotide in more than 2,000 patients reveal important correlations to ziconotides non-clinical pharmacology. For example, ziconotide provides significant pain relief to severe chronic pain sufferers who have failed to obtain relief from opiate therapy and no evidence of tolerance to ziconotide is seen in these patients. Contingent on regulatory approval, ziconotide will be the first in a new class of neurological drugs: the N-type calcium channel blockers, or NCCBs. Its novel mechanism of action as a non-opioid analgesic suggests ziconotide has the potential to play a valuable role in treatment regimens for severe chronic pain. If approved for clinical use, ziconotide will further validate the neuroactive venom peptides as a source of new and useful medicines.
Export Options
About this article
Cite this article as:
Miljanich P. G., Ziconotide: Neuronal Calcium Channel Blocker for Treating Severe Chronic Pain, Current Medicinal Chemistry 2004; 11 (23) . https://dx.doi.org/10.2174/0929867043363884
DOI https://dx.doi.org/10.2174/0929867043363884 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Pharmacokinetic Drug-drug Interaction of Antibiotics Used in Sepsis Care in China
Current Drug Metabolism Targeting the Immune System in Cancer
Current Pharmaceutical Biotechnology Effect of Grapefruit Juice in Relation to Human Pharmacokinetic Study
Current Clinical Pharmacology Coronary Risk Factors in the Elderly: Their Interactions and Treatment
Current Pharmaceutical Design Pathophysiology of Sepsis in the Elderly: Clinical Impact and Therapeutic Considerations
Current Drug Targets Intravitreal Anti-VEGF Drugs as Adjuvant Therapy in Diabetic Retinopathy Surgery
Current Diabetes Reviews When and How Should We Cover Patients for Community-Acquired Methicillin-Resistant Staphylococcus aureus (MRSA) Pneumonia?
Current Respiratory Medicine Reviews The Effect of Sex and Gender on Diabetic Complications
Current Diabetes Reviews Pharmacology of Adenosine A2A Receptors and Therapeutic Applications
Current Topics in Medicinal Chemistry Phosphodiesterase 5 Inhibitors - Drug Design and Differentiation Based on Selectivity, Pharmacokinetic and Efficacy Profiles
Current Pharmaceutical Design Safe and Effective Delivery of Amphotericin B: A Survey of Patents
Recent Patents on Nanotechnology Will Medicinal Cannabinoids Prove to be Useful Clinically?
Current Drug Therapy Bioactive Cyclohexenones: A Mini Review
Current Bioactive Compounds Kinin Receptors in Vascular Biology and Pathology
Current Vascular Pharmacology Antioxidant Capacity of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles
Letters in Drug Design & Discovery Current Advances in Therapy for Metastatic Melanoma
Current Cancer Therapy Reviews Midazolam Plus Haloperidol as Adjuvant Analgesics to Morphine in Opium Dependent Patients: A Randomized Clinical Trial
Current Drug Abuse Reviews Synthesis and Biological Activity of Quaternary Quinolinium Salts: A Review
Current Organic Chemistry Developing Specific Therapeutic Strategies for Transfusion-Related Acute Lung Injury. An Overview of Potentially Useful Animal Models
Cardiovascular & Hematological Agents in Medicinal Chemistry An Inducible Expression System for Recombinant Sca Proteins with an Autotransporter Domain from <i>Orientia Tsutsugamushi in Escherichia coli</i>
Protein & Peptide Letters