Abstract
We found that zonisamide (ZNS) has beneficial effects on Parkinsons disease (PD). ZNS is originally synthesized in Japan and has been used for over 10 years to treat intractable epilepsy. We administered 300 mg of ZNS to a patient with PD who incidentally had convulsive attacks. The attacks disappeared and, surprisingly, the parkinsonian symptoms improved dramatically. An open trial of ZNS (given in addition to their anti-PD drugs) in advanced PD patients clearly showed the lessening of symptoms, especially wearing-off. Although the effects gradually decreased after 1.5 years, more than 30% improvement of UPDRS total score was maintained up to 3 years. Nation-wide double-blind controlled study confirmed that the small dose (50mg / day) of ZNS improved all the cardinal symptoms of PD. As for its mechanism, we showed that ZNS increases dopamine contents in the striatum by activating dopamine synthesis and the level of mRNA of tyrosine hydroxylase (TH) prior to that of TH protein. ZNS moderately inhibits monoamine oxydase (MAO) B. It has no effects on dopamine receptors, dopamine transporter or dopamine release. ZNS has no direct effects on glutamate receptors, adenosine receptors, or serotonergic system, which have been suggested to be effective points of anti-PD drug other than dopamine system. Therefore, it is suggested that the activation of dopamine synthesis and the moderate level of MAOB inhibition are main mechanisms of ZNS effects on PD. ZNS has significant effects on T-type Ca++ channels and oxidative stress. They may also affect the beneficial action of ZNS on PD.
Keywords: zonisamide, parkinsons disease, wearing-off, dopamine, tyrosine hydroxylase, t-type, oxidative stress
Current Pharmaceutical Design
Title: Novel Therapeutic Effects of the Anti-Convulsant, Zonisamide, on Parkinsons Disease
Volume: 10 Issue: 6
Author(s): M. Murata
Affiliation:
Keywords: zonisamide, parkinsons disease, wearing-off, dopamine, tyrosine hydroxylase, t-type, oxidative stress
Abstract: We found that zonisamide (ZNS) has beneficial effects on Parkinsons disease (PD). ZNS is originally synthesized in Japan and has been used for over 10 years to treat intractable epilepsy. We administered 300 mg of ZNS to a patient with PD who incidentally had convulsive attacks. The attacks disappeared and, surprisingly, the parkinsonian symptoms improved dramatically. An open trial of ZNS (given in addition to their anti-PD drugs) in advanced PD patients clearly showed the lessening of symptoms, especially wearing-off. Although the effects gradually decreased after 1.5 years, more than 30% improvement of UPDRS total score was maintained up to 3 years. Nation-wide double-blind controlled study confirmed that the small dose (50mg / day) of ZNS improved all the cardinal symptoms of PD. As for its mechanism, we showed that ZNS increases dopamine contents in the striatum by activating dopamine synthesis and the level of mRNA of tyrosine hydroxylase (TH) prior to that of TH protein. ZNS moderately inhibits monoamine oxydase (MAO) B. It has no effects on dopamine receptors, dopamine transporter or dopamine release. ZNS has no direct effects on glutamate receptors, adenosine receptors, or serotonergic system, which have been suggested to be effective points of anti-PD drug other than dopamine system. Therefore, it is suggested that the activation of dopamine synthesis and the moderate level of MAOB inhibition are main mechanisms of ZNS effects on PD. ZNS has significant effects on T-type Ca++ channels and oxidative stress. They may also affect the beneficial action of ZNS on PD.
Export Options
About this article
Cite this article as:
Murata M., Novel Therapeutic Effects of the Anti-Convulsant, Zonisamide, on Parkinsons Disease, Current Pharmaceutical Design 2004; 10 (6) . https://dx.doi.org/10.2174/1381612043453180
DOI https://dx.doi.org/10.2174/1381612043453180 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Pathophysiology of Status Epilepticus Induced by Pilocarpine
Central Nervous System Agents in Medicinal Chemistry Are Antipsychotics Useful in the Treatment of Anorexia Nervosa? A Review of the Literature
Current Psychopharmacology A Review on the Phytochemicals, Ethnomedicine Uses and Pharmacology of Ficus Species
Current Traditional Medicine Omega-3 Fatty Acids and their Role in Central Nervous System - A Review
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Aging Science Melatonin, its Metabolites and its Synthetic Analogs as Multi-Faceted Compounds: Antioxidant, Prooxidant and Inhibitor of Bioactivation Reactions
Current Medicinal Chemistry Relevance of Breast Cancer Resistance Protein to Brain Distribution and Central Acting Drugs: A Pharmacokinetic Perspective
Current Drug Metabolism Patent Selections:
Recent Patents on CNS Drug Discovery (Discontinued) Dangerous Liaisons: Tau Interaction with Muscarinic Receptors
Current Alzheimer Research Management of Incidental Findings in the Era of Next-generation Sequencing
Current Genomics Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies
Current Neuropharmacology The NMDA Receptor Complex: A Promising Target for Novel Antiepileptic Strategies
Current Medicinal Chemistry Effects on the Post-translational Modification of H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 Levels in Cerebral Cortex, Hypothalamus and Pons of Rats after a Systemic Administration of Cannabidiol: A Preliminary Study
Central Nervous System Agents in Medicinal Chemistry Imidazole: An Essential Edifice for the Identification of New Lead Compounds and Drug Development
Mini-Reviews in Medicinal Chemistry How Accurate is Subjective Reporting of Childhood Sleep Patterns? A Review of the Literature and Implications for Practice
Current Pediatric Reviews GABAA Receptors, Anesthetics and Anticonvulsants in Brain Development
CNS & Neurological Disorders - Drug Targets Increased Epileptiform EEG Activity and Decreased Seizure Threshold in Arctic APP Transgenic Mouse Model of Alzheimer’s Disease
Current Alzheimer Research Localised Delivery of Therapeutic Agents to CNS Malignancies: Old and New Approaches
Current Pharmaceutical Biotechnology Genetics of Serotonin Receptors and Depression: State of the Art
Current Drug Targets Probenecid: An Emerging Tool for Neuroprotection
CNS & Neurological Disorders - Drug Targets