Cargando…

Zonisamide for the Treatment of Parkinson Disease: A Current Update

Zonisamide has been used as an add-on treatment in order to overcome the deficiencies of the general therapies currently used to resolve the motor complications and non-motor symptoms of Parkinson disease. Various trials have been designed to investigate the mechanism of action and treatment effects...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Chengqian, Xue, Li, Liu, Yumei, Yang, Zhengjie, Chi, Song, Xie, Anmu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779619/
https://www.ncbi.nlm.nih.gov/pubmed/33408605
http://dx.doi.org/10.3389/fnins.2020.574652
_version_ 1783631371129847808
author Li, Chengqian
Xue, Li
Liu, Yumei
Yang, Zhengjie
Chi, Song
Xie, Anmu
author_facet Li, Chengqian
Xue, Li
Liu, Yumei
Yang, Zhengjie
Chi, Song
Xie, Anmu
author_sort Li, Chengqian
collection PubMed
description Zonisamide has been used as an add-on treatment in order to overcome the deficiencies of the general therapies currently used to resolve the motor complications and non-motor symptoms of Parkinson disease. Various trials have been designed to investigate the mechanism of action and treatment effects of zonisamide in this condition. Most clinical trials of zonisamide in Parkinson disease were from Japan. The vast majority of studies used changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) scores and daily “OFF” time as primary endpoints. Based on adequate randomized controlled trials, zonisamide is considered a safe and efficacious add-on treatment in Parkinson disease. The most convincing proof is available for a dosage of 25–50 mg, which was shown to lead to a significant reduction in the UPDRS III score and daily “OFF” time, without increasing disabling dyskinesia. Furthermore, zonisamide may play a beneficial role in improving non-motor symptoms in PD, including impulsive–compulsive disorder, rapid eye movement sleep behavior disorder, and dementia. Among the various mechanisms reported, inhibition of monoamine oxidase-B, blocking of T-type calcium channels, modulation of the levodopa–dopamine metabolism, modulation of receptor expression, and neuroprotection are the most often cited. The mechanisms underlying neuroprotection, including modulation of dopamine turnover, induction of neurotrophic factor expression, inhibition of oxidative stress and apoptosis, inhibition of neuroinflammation, modulation of synaptic transmission, and modulation of gene expression, have been most extensively studied. This review focuses on structure, pharmacokinetics, mechanisms, therapeutic effectiveness, and safety and tolerability of zonisamide in patients with Parkinson disease.
format Online
Article
Text
id pubmed-7779619
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-77796192021-01-05 Zonisamide for the Treatment of Parkinson Disease: A Current Update Li, Chengqian Xue, Li Liu, Yumei Yang, Zhengjie Chi, Song Xie, Anmu Front Neurosci Neuroscience Zonisamide has been used as an add-on treatment in order to overcome the deficiencies of the general therapies currently used to resolve the motor complications and non-motor symptoms of Parkinson disease. Various trials have been designed to investigate the mechanism of action and treatment effects of zonisamide in this condition. Most clinical trials of zonisamide in Parkinson disease were from Japan. The vast majority of studies used changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) scores and daily “OFF” time as primary endpoints. Based on adequate randomized controlled trials, zonisamide is considered a safe and efficacious add-on treatment in Parkinson disease. The most convincing proof is available for a dosage of 25–50 mg, which was shown to lead to a significant reduction in the UPDRS III score and daily “OFF” time, without increasing disabling dyskinesia. Furthermore, zonisamide may play a beneficial role in improving non-motor symptoms in PD, including impulsive–compulsive disorder, rapid eye movement sleep behavior disorder, and dementia. Among the various mechanisms reported, inhibition of monoamine oxidase-B, blocking of T-type calcium channels, modulation of the levodopa–dopamine metabolism, modulation of receptor expression, and neuroprotection are the most often cited. The mechanisms underlying neuroprotection, including modulation of dopamine turnover, induction of neurotrophic factor expression, inhibition of oxidative stress and apoptosis, inhibition of neuroinflammation, modulation of synaptic transmission, and modulation of gene expression, have been most extensively studied. This review focuses on structure, pharmacokinetics, mechanisms, therapeutic effectiveness, and safety and tolerability of zonisamide in patients with Parkinson disease. Frontiers Media S.A. 2020-12-21 /pmc/articles/PMC7779619/ /pubmed/33408605 http://dx.doi.org/10.3389/fnins.2020.574652 Text en Copyright © 2020 Li, Xue, Liu, Yang, Chi and Xie. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Li, Chengqian
Xue, Li
Liu, Yumei
Yang, Zhengjie
Chi, Song
Xie, Anmu
Zonisamide for the Treatment of Parkinson Disease: A Current Update
title Zonisamide for the Treatment of Parkinson Disease: A Current Update
title_full Zonisamide for the Treatment of Parkinson Disease: A Current Update
title_fullStr Zonisamide for the Treatment of Parkinson Disease: A Current Update
title_full_unstemmed Zonisamide for the Treatment of Parkinson Disease: A Current Update
title_short Zonisamide for the Treatment of Parkinson Disease: A Current Update
title_sort zonisamide for the treatment of parkinson disease: a current update
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779619/
https://www.ncbi.nlm.nih.gov/pubmed/33408605
http://dx.doi.org/10.3389/fnins.2020.574652
work_keys_str_mv AT lichengqian zonisamideforthetreatmentofparkinsondiseaseacurrentupdate
AT xueli zonisamideforthetreatmentofparkinsondiseaseacurrentupdate
AT liuyumei zonisamideforthetreatmentofparkinsondiseaseacurrentupdate
AT yangzhengjie zonisamideforthetreatmentofparkinsondiseaseacurrentupdate
AT chisong zonisamideforthetreatmentofparkinsondiseaseacurrentupdate
AT xieanmu zonisamideforthetreatmentofparkinsondiseaseacurrentupdate