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 ex ogenous nitroxide radicals, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-ox yl (carbamoyl-PROXYL) and 3-methoxy carbonyl-2,2,5,5-tetramethylpyrrolidine -1-oxyl (PCAM). Time-dependent changes in the signal intensities of these e xogenous nitroxide radicals obtained from the hippocampal perfusates were o bserved using an X-band ESR spectrometer at 20-min intervals. The ESR signa l intensities of nitroxide radicals decreased exponentially in all animals, which indicates that their half-life could be used as a parameter to estim ate the decay rate of nitroxide radicals. Nitroxide radicals lose their par a magnetism when exposed to reductants in a biological system. Thus, half-l ife reflects the in vivo reducing ability. Although the half-life of carbam oyl-PROXYL, which could not pass the blood-brain barrier (BBB), was not cha nged when compared with the controls, pre-treatment with ZNS significantly shortened the half-life of PCAM, which could pass through the BBB. These fi ndings suggest that the ZNS-induced increase in reducing ability did not oc cur within the extracellular space, but rather mainly at the neural cell me mbrane, This study is the first in vivo evaluation of the reducing ability of ZNS in freely moving animals.