Therapeutic effect of a novel anti-parkinsonian agent zonisamide against MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) neurotoxicity in mice

Yokoyama, Hironori; Yano, Ryohei; Kuroiwa, Hayato; Tsukada, Tatsuya; Uchida, Hiroto; Kato, Harubumi; Kasahara, Jiro; Araki, Tsutomu

doi:10.1007/s11011-010-9212-z

Cited by 16 publications

(15 citation statements)

References 35 publications

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“…ZNS increases glutathione levels and inhibits striatal levodopa‐induced quinone formation . In ZNS, further neuroprotective effects are reported, such as Mn superoxide dismutase enhancement, inhibition of microglial activation and increase of TH‐positive neurons mediated with S100β secretion . All this evidence supports the scientific validity of our study focusing on early use of ZNS in PD.…”

Section: Discussionsupporting

confidence: 82%

Zonisamide in the early stage of Parkinson's disease

Maeda

Takano

Yamazaki

et al. 2015

Neurology & Clinical Neurosc

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Background Zonisamide is one of the anti‐parkinsonian agents approved and used in Japan, and it improves motor symptoms and off time in the advanced stage of Parkinson's disease. However, there is no evidence of its efficacy in the early stage of Parkinson's disease. Aim To investigate the effect of zonisamide on the early stage of Parkinson's disease. Methods We consecutively recruited patients with less than 3 years of disease duration who were treated with levodopa/dopa decarboxylase inhibitor only or additional small amounts of dopamine agonists. We evaluated motor severities with the Unified Parkinson's Disease Rating Scale, non‐motor severities with the Non‐Motor Symptom scale and health‐related quality of daily life with the 39 items of the Parkinson's Disease Questionnaire. Patients also evaluated themselves with the Patient Global Impression of Improvement index. Serum zonisamide levels were monitored throughout the study. After the baseline clinical evaluation, patients received 25 mg of open‐label zonisamide, and were evaluated for 28 weeks. Results We recruited 13 patients, and 11 patients completed the study. Adjunctive zonisamide significantly improved the Unified Parkinson's Disease Rating Scale part III score and Patient Global Impression of Improvement after the 12th week. The Non‐Motor Symptom Scale and summary index of the 39‐item Parkinson's Disease Questionnaire showed no significant changes. Mean plasma levels of zonisamide were stable throughout the study. Two patients could not complete because of adverse events. Conclusions Zonisamide can be expected to be safe and beneficial to motor symptoms of Parkinson's disease in the early stage as well as the advanced stage.

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Section: Discussionsupporting

confidence: 82%

Zonisamide in the early stage of Parkinson's disease

Maeda

Takano

Yamazaki

et al. 2015

Neurology & Clinical Neurosc

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“…ZNS, indeed, up- regulates manganese-superoxide dismutase (MnSOD) and inhibits monoamine oxidase B (MAO-B). These pharmacological effects contribute in protecting dopaminergic neurons from MTPT toxicity [115-118] and human neuroblastoma SHSY5Y cells from staurosporine-induced apoptosis [119]. Astrocytes could be responsible for ZNS neuroprotection.…”

Section: Introductionmentioning

confidence: 99%

The Changing Landscape of Voltage-Gated Calcium Channels in Neurovascular Disorders and in Neurodegenerative Diseases

Cataldi

2013

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It is a common belief that voltage-gated calcium channels (VGCC) cannot carry toxic amounts of Ca2+ in neurons. Also, some of them as L-type channels are essential for Ca2+-dependent regulation of prosurvival gene-programs. However, a wealth of data show a beneficial effect of drugs acting on VGCCs in several neurodegenerative and neurovascular diseases. In the present review, we explore several mechanisms by which the “harmless” VGCCs may become “toxic” for neurons. These mechanisms could explain how, though usually required for neuronal survival, VGCCs may take part in neurodegeneration. We will present evidence showing that VGCCs can carry toxic Ca2+ when: a) their density or activity increases because of aging, chronic hypoxia or exposure to β-amyloid peptides or b) Ca2+-dependent action potentials carry high Ca2+ loads in pacemaker neurons. Besides, we will examine conditions in which VGCCs promote neuronal cell death without carrying excess Ca2+. This can happen, for instance, when they carry metal ions into the neuronal cytoplasm or when a pathological decrease in their activity weakens Ca2+-dependent prosurvival gene programs. Finally, we will explore the role of VGCCs in the control of nonneuronal cells that take part to neurodegeneration like those of the neurovascular unit or of microglia.

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“…[41] It has been observed in a study by Yokoyama et al ., that zonisamide causes an inhibition of microglial activation and hence may slow the progression of the disease. [42] They investigated the effect of zonisamide on MPTP induced neurotoxicity in mice. The study concluded that zonisamide prevented the depletion of TH and prevents the proliferation of microglia in the striatum and substantia nigra.…”

Section: Introductionmentioning

confidence: 99%

“…[32] Zonisamide has been shown to increase the DA synthesis by increasing the tyrosine hydroxylase activity in the striatum. [4243] In the study by Gluck et al , zonisamide was tested in a cerebral microdialysis system in 6OHDA nigrotomized rats. DA and dopaminergic metabolites were increased when zonisamide was administered with levodopa and carbidopa.…”

Section: Introductionmentioning

confidence: 99%

“…[44] Increase in TH content and an increase in DA turnover has also been documented with several other studies (Yokoyama 2010, Kubo 2008; Yabe 2009;Yamamura 2009;). [42454647] Murakami et al ., had demonstrated in a study in 2001 that zonisamide has a biphasic, concentration dependent effect on the exocytosis of dopamine. [48] However, the dose at which this effect was seen was equivalent to antiepileptic doses of zonismaide and increasing the dose beyond that inhibits the release of dopamine.…”

Section: Introductionmentioning

confidence: 99%

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Zonisamide: A review of the clinical and experimental evidence for its use in Parkinson′s disease

et al. 2013

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The limitations of currently available therapies in addressing the non motor symptoms of Parkinson's disease (PD) have egged on the search for newer options. Zonisamide has been in use for epilepsy and it was serendipitously found to improve the symptoms of PD in a patient who had both epilepsy and PD. Thereafter, various trials were designed to assess the use of zonisamide in PD. The present article investigates the evidence for use of zonisamide in PD from the various clinical trials that were designed to address this issue. Furthermore, the article also summarizes the various mechanisms of its use in PD as described in various animal experiments. A search protocol was designed with predefined inclusion and exclusion criteria. The databases searched were Pubmed, Ovid medline, Cochrane and clinicaltrials.gov. The data thus generated, was fed into a predesigned format. Most of the clinical trials on zonisamide in PD have come from Japan. Most of these trials used the changes in the Unified Parkinson's Disease Rating Scale (UPDRS) score as the endpoints and the most conclusive evidence is for a dose of 25-50 mg, which caused a change in UPDRS part III (motor symptoms). These patients were on levodopa and other drugs used for PD during the trials. One of the clinical trials conducted in Spain investigates the use of zonisamide in impulse control disorders among 15 patients of PD. Among the many mechanisms postulated, a reduction in levodopa induced quinone formation, protection against mitochondrial impairment and an increase in astroglial cysteine transport, an inhibition of microglial activation, monoamine oxidase-B (MAO-B) inhibition, an increased dopamine release and blockade of calcium channels are the most cited. There is evidence for use of zonisamide in PD in addition to levodopa and other therapies for control of motor symptoms. For now, the evidence for its use in control of non motor symptoms in PD is not enough and needs to be investigated further.

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Therapeutic effect of a novel anti-parkinsonian agent zonisamide against MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) neurotoxicity in mice

Cited by 16 publications

References 35 publications

Zonisamide in the early stage of Parkinson's disease

Zonisamide in the early stage of Parkinson's disease

The Changing Landscape of Voltage-Gated Calcium Channels in Neurovascular Disorders and in Neurodegenerative Diseases

Zonisamide: A review of the clinical and experimental evidence for its use in Parkinson′s disease

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