Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP.
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.
Yabe
Hayato
H
Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan.
Choudhury
Mohammed Emamussalehin
ME
Kubo
Madoka
M
Nishikawa
Noriko
N
Nagai
Masahiro
M
Nomoto
Masahiro
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001679:Biogenic Amines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002144:Callithrix; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D006719:Homovanillic Acid / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D000078305:Zonisamide
D000927:Anticonvulsants; D001679:Biogenic Amines; D015259:Dopamine Agents; D007555:Isoxazoles; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D000078305:Zonisamide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D004298:Dopamine; D006719:Homovanillic Acid