Zonisamide attenuates MPTP neurotoxicity in marmosets

Mptp (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces parkinsonism in humans and animals. the effects of zonisamide on dopamine neurons were studied in mptp-treated common marmosets (callithrix jacchus). groups of animals (n = 3) 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 (a known mao-b inhibitor) (2 mg/kg administered 1 h before each mptp dose); and saline controls. an immunohistochemical study of the substantia nigra was performed 14 days after mptp treatment in each group. mptp reduced the mean number of tyrosine hydroxylase (th)-positive neurons to 10% of the normal control group and mean cell size was significantly (p < 0.001) reduced from 424 to 159 μm 2. in the group pre-treated with zonis amide,the mean number of th-positive neurons was reduced to 26% of that in the normal control group and the mean neuron size was significantly (p < 0.05) increased from 159 to 273 μm 2 compared with the group treated with mptp alone. moreover,in the group pre-treated with selegiline,the mean number of th-positive neurons was 47% of that in the normal control group and the mean neuron size was increased significantly (p < 0.01) from159 to 319 μm 2 compared to the group treated with mptp alone. this observation suggests that zonisamide reduces mptp toxicity. © 2010 the japanese pharmacological society.