In vivo evaluation of hippocampal anti-oxidant ability of zonisamide in rats.
We evaluated the anti-oxidant property of zonisamide (ZNS) in the rat brain under freely moving conditions by means of in vivo microdialysis of two exogenous nitroxide radicals, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) and 3-methoxy carbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM). Time-dependent changes in the signal intensities of these exogenous nitroxide radicals obtained from the hippocampal perfusates were observed using an X-band ESR spectrometer at 20-min intervals. The ESR signal intensities of nitroxide radicals decreased exponentially in all animals, which indicates that their half-life could be used as a parameter to estimate the decay rate of nitroxide radicals. Nitroxide radicals lose their paramagnetism when exposed to reductants in a biological system. Thus, half-life reflects the in vivo reducing ability. Although the half-life of carbamoyl-PROXYL, which could not pass the blood-brain barrier (BBB), was not changed when compared with the controls, pre-treatment with ZNS significantly shortened the half-life of PCAM, which could pass through the BBB. These findings suggest that the ZNS-induced increase in reducing ability did not occur within the extracellular space, but rather mainly at the neural cell membrane. This study is the first in vivo evaluation of the reducing ability of ZNS in freely moving animals.
Tokumaru
J
J
Department of Psychiatry, Miyazaki Medical College, Kiyotake, Japan.
Ueda
Y
Y
Yokoyama
H
H
Nakajima
A
A
Doi
T
T
Mitsuyama
Y
Y
Ohya-Nishiguchi
H
H
Kamada
H
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D011759:Pyrrolidines / Q000493:pharmacokinetics; D011837:Radiation-Protective Agents / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D000078305:Zonisamide
D000975:Antioxidants; D003497:Cyclic N-Oxides; D007555:Isoxazoles; C109806:MCPROXYL; D011759:Pyrrolidines; D011837:Radiation-Protective Agents; D013113:Spin Labels; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl; D000078305:Zonisamide