Zonisamide Increases Dopamine Turnover in the Striatum of Mice and Common Marmosets Treated With MPTP

Journal of Pharmacological Sciences

Madoka Kubo¹  Noriko Nishikawa¹  Hayato Yabe¹  Masahiro Nomoto¹  Masahiro Nagai¹  Mohammed Emamussalehin Choudhury¹ 

[1] Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan

关键词: zonisamide;    dopamine;    MPTP;    common marmoset;   

DOI  :  10.1254/jphs.09019FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(24)Cited-By(14)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 ×4); 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 ×4); and saline controls. Groups of common marmosets (n = 4 – 6) were treated with: MPTP (2.5 mg/kg every 24 h ×3); 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.

【 授权许可】

Unknown