Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP.

Full Abstract

The effect of zonisamide, an antiepileptic agent with anti-parkinsonian effects, was studied on dopamine neurons of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 mice and common marmosets. Groups of mice (n = 8 - 9) were treated with: MPTP (15 mg/kg every 2 h x4); MPTP plus zonisamide (40 mg/kg administered 1 h before each MPTP dose); MPTP plus selegiline (2 mg/kg administered 1 h before the first MPTP dose); zonisamide (40 mg/kg x4); and saline controls. Groups of common marmosets (n = 4 - 6) were treated with: MPTP (2.5 mg/kg every 24 h x3); MPTP plus zonisamide (40 mg/kg administered 1 h before each MPTP dose); MPTP plus selegiline (2 mg/kg administered 1 h before the first MPTP dose); and saline controls. Brain dopamine and its metabolites were determined by HPLC. Dopamine content decreased in the striatum of MPTP-treated mice and monkeys. Co-administration of selegiline inhibited the effect of MPTP and dopamine contents were similar to those of the controls. Co-administration of zonisamide did not inhibit the effect of MPTP on dopamine content, but increased striatal dopamine turnover of animals treated with MPTP plus zonisamide more than in those treated with MPTP alone. MPTP treatment caused a compensatory increase of dopamine turnover in the striatum by remaining neurons. Zonisamide may help dopaminergic neurons by increasing striatal dopamine turnover following MPTP treatment.

Author information

Author/s: Yabe, Hayato (H); Choudhury, Mohammed Emamussalehin (ME); Kubo, Madoka (M); Nishikawa, Noriko (N); Nagai, Masahiro (M); Nomoto, Masahiro (M);

Affiliation: Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of pharmacological sciences (J Pharmacol Sci), published in Japan. (Language: eng)

Reference: 2009-May; vol 110 (issue 1) : pp 64-8

Dates: Created 2009/05/15; Completed 2009/07/02;

PMID: 19403994, status: MEDLINE (last retrieval date: 7/2/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology
3,4-Dihydroxyphenylacetic Acid - metabolism
Animals
Anticonvulsants - pharmacology
Biogenic Amines - metabolism
Brain Chemistry - drug effects
Callithrix
Dopamine - metabolism; physiology
Dopamine Agents - pharmacology
Dyskinesia, Drug-Induced - physiopathology

Homovanillic Acid - metabolism
Isoxazoles - pharmacology
Male
Mice
Mice, Inbred C57BL
Monoamine Oxidase - metabolism
Monoamine Oxidase Inhibitors - pharmacology
Neostriatum - drug effects; metabolism
Neurons - drug effects; metabolism
Selegiline - pharmacology

Associated Chemicals: Anticonvulsants (0) ; Biogenic Amines (0) ; Dopamine Agents (0) ; Isoxazoles (0) ; Monoamine Oxidase Inhibitors (0) ; 3,4-Dihydroxyphenylacetic Acid (102-32-9) ; Selegiline (14611-51-9) ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (28289-54-5) ; Homovanillic Acid (306-08-1) ; zonisamide (68291-97-4) ; Monoamine Oxidase (EC 1.4.3.4)

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