The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance.

Experimental Neurology
Patricia K SonsallaBrian Buckley

Abstract

Zonisamide is an FDA-approved antiepileptic drug that blocks voltage-dependent Na(+) channels and T-type Ca(2+) channels and improves clinical outcome in Parkinson's disease (PD) patients when used as an adjunct to other PD therapies. Zonisamide also modifies dopamine (DA) activity, provides protection in ischemia models and influences antioxidant systems. Thus, we tested it for its ability to protect DA neurons in a mouse model of PD and investigated mechanisms underlying its protection. Concurrent treatment of mice with zonisamide and 1-methyl-4-phenyl-1,2,3,6-tetraydropyridine (MPTP) attenuated the reduction in striatal contents of DA, its metabolite DOPAC and tyrosine hydroxylase (TH). We also discovered that zonisamide inhibited monoamine oxidase B (MAO-B) activity in vitro with an IC(50) of 25 muM, a concentration that is well within the therapeutic range used for treating epilepsy in humans. Moreover, the irreversible binding of systemically administered selegiline to MAO-B in mouse brain was attenuated by zonisamide as measured by ex vivo assays. Zonisamide treatment alone did not produce any lasting effects on ex vivo MAO-B activity, indicating that it is a reversible inhibitor of the enzyme. Consistent with the effect...Continue Reading

References

Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R E HeikkilaT P Singer
Jun 1, 1996·Seizure : the Journal of the British Epilepsy Association·M KitoK Watanabe
Nov 1, 1995·Epilepsy Research·M OkadaY Fukushima
Dec 16, 1998·Therapeutic Drug Monitoring·T Mimaki
Apr 15, 1999·Annual Review of Neuroscience·J C ShihM J Ridd
Oct 31, 2000·Neurochemical Research·J TokumaruH Kamada
May 4, 2004·Journal of Ethnopharmacology·L D KongR X Tan
Jan 11, 2005·Current Topics in Medicinal Chemistry·Piotr CzapińskiStanislaw J Czuczwar
Feb 7, 2006·Bioorganic & Medicinal Chemistry·Ashraf A KhalilNeal Castagnoli
Jan 3, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Brian S Meldrum, Michael A Rogawski
Jan 4, 2007·Neurology·Miho MurataUNKNOWN Japan Zonisamide on PD Study Group
Feb 21, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Ming YangJohn C Shryock
Sep 1, 2007·Clinical Neuropharmacology·Victor Biton
Oct 17, 2007·Environmental Health Perspectives·Kavita PrasadEric K Richfield
May 1, 2009·Journal of Pharmacological Sciences·Hayato YabeMasahiro Nomoto

❮ Previous
Next ❯

Citations

Feb 25, 2014·Pflügers Archiv : European journal of physiology·Benjamin J KopeckyJianxin Bao
Dec 19, 2013·Indian Journal of Pharmacology·Neeta D GroverTatyasaheb R Patil
Oct 22, 2013·Neurochemical Research·Salvatore CondelloFrancesco Pisani
Jan 28, 2012·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Takafumi SaiHiroyuki Nakayama
Jul 30, 2011·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Takafumi SaiHiroyuki Nakayama
Oct 18, 2015·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Kelly E DunnAnnie Umbricht
Jun 23, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Miho MurataUNKNOWN Japan Zonisamide on PD Study Group
Nov 9, 2010·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Dae-Hee LeeYong J Lee
May 15, 2013·The Journal of Toxicological Sciences·Takafumi SaiHiroyuki Nakayama
Jun 1, 2013·Journal of Toxicologic Pathology·Takafumi SaiHiroyuki Nakayama
Apr 22, 2015·CNS Drugs·Christopher J HammondAlbert J Arias
Mar 1, 2015·Neurotoxicology·Guadalupe PalenciaJulio Sotelo
May 11, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Tomás Herraiz, Hugo Guillén
Jun 5, 2012·European Journal of Pharmacology·M E ChoudhuryM Nomoto
May 11, 2010·Experimental Neurology·Thomas W RöslerGünter U Höglinger
Feb 16, 2011·Brain Research·Mohammed Emamussalehin ChoudhuryMasahiro Nomoto
Oct 16, 2010·Journal of Pharmacological Sciences·Mohammed Emamussalehin ChoudhuryMasahiro Nomoto
Jul 22, 2014·Chembiochem : a European Journal of Chemical Biology·Werner J GeldenhuysMi Hee Lim
May 2, 2020·Journal of Human Genetics·Pei-Chieng ChaTatsushi Toda
Oct 28, 2017·Frontiers in Pharmacology·Yuhei NishimuraHideaki Hara
Nov 16, 2016·Scientific Reports·Santiago VilarGeorge Hripcsak
Oct 7, 2020·Expert Opinion on Pharmacotherapy·Francesco PanzaBruno P Imbimbo
Sep 21, 2019·Bioorganic & Medicinal Chemistry Letters·Anton ShetnevJacobus P Petzer
Jan 29, 2021·Expert Review of Neurotherapeutics·Peter JennerRobert A Hauser
Jan 8, 2021·Frontiers in Neuroscience·Chengqian LiAnmu Xie
May 13, 2021·Drug Design, Development and Therapy·Babak Tousi, James B Leverenz
Aug 28, 2021·International Journal of Molecular Sciences·Kaneyasu Nishimura, Kazuyuki Takata

❮ Previous
Next ❯

Related Concepts

Related Feeds

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.