Hori M, Ito T, Oka M, Noda Y, Matsuno Y, Furukawa K, Ochi Y, Karasawa T, Kadokawa T
Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Arzneimittelforschung. 1987 Oct;37(10):1124-30.
The effects of 1,2-benzisoxazole-3-methanesulfonamide (zonisamide, AD-810, CI-912), an antiepileptic compound, on the central nervous system were compared with those of carbamazepine and acetazolamide in experimental animals. 1. Zonisamide at an oral dose of 100 mg/kg was without effect on general behavior in mice except lowerings of pelvic, tail and body positions and ptosis. In rats, zonisamide slightly decreased the body temperature at the same dose. 2. Zonisamide (50 mg/kg p.o.) did not affect spontaneous alteration behavior and active avoidance performance in mice, although it impaired the acquisition of step-down passive avoidance behavior in mice. Carbamazepine (50 mg/kg) deteriorated the spontaneous alternation behavior. 3. Zonisamide (40 mg/kg i.v.) did not affect the relative power of cortical EEGs in gallamine-immobilized cats. Caudate spindles and recruiting responses, induced by electrical stimulation of the head of the caudate nucleus and the ventralis anterior thalamus, respectively, were not affected with the same dose of zonisamide in cats. On the other hand, carbamazepine (5 mg/kg) decreased the beta 2 relative power in the cortex, and enhanced both caudate spindles and recruiting responses. 4. Zonisamide (10 mg/kg i.v.) and carbamazepine (3 mg/kg) showed a tendency to depress the flexor reflex without affecting the neuromuscular transmission in anesthetized cats. 5. The central effects of zonisamide clearly differed from those of acetazolamide. Namely, acetazolamide markedly decreased brain pH at 25 mg/kg i.v., and increased regional cerebral blood flow at 100 mg/kg p.o. in rats. Zonisamide at 50 mg/kg i.v. and 100 mg/kg p.o. did not affect brain pH and regional cerebral blood flow, respectively. In addition, zonisamide (100 mg/kg p.o.) decreased brain contents of dopamine metabolite, DOPAC, with slight increase of a serotonin metabolite, 5-HIAA, in mice, and decreased brain contents of dopamine metabolites, DOPAC and HVA, in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
在实验动物中，将抗癫痫化合物1,2 - 苯并异恶唑 - 3 - 甲磺酰胺（唑尼沙胺，AD - 810，CI - 912）对中枢神经系统的作用与卡马西平和乙酰唑胺的作用进行了比较。1. 口服剂量为100 mg/kg的唑尼沙胺对小鼠的一般行为无影响，仅使骨盆、尾巴和身体姿势降低以及出现眼睑下垂。在大鼠中，相同剂量的唑尼沙胺会使体温略有下降。2. 唑尼沙胺（口服50 mg/kg）不影响小鼠的自发交替行为和主动回避表现，尽管它会损害小鼠的逐步递减被动回避行为的习得。卡马西平（50 mg/kg）会使自发交替行为恶化。3. 唑尼沙胺（静脉注射40 mg/kg）对加兰他敏固定的猫的皮质脑电图相对功率无影响。分别由尾状核头部和丘脑腹前核电刺激诱导的尾状核纺锤波和募集反应，在相同剂量的唑尼沙胺作用下，猫未受影响。另一方面，卡马西平（5 mg/kg）会降低皮质中的β2相对功率，并增强尾状核纺锤波和募集反应。4. 唑尼沙胺（静脉注射10 mg/kg）和卡马西平（3 mg/kg）在麻醉猫中显示出抑制屈肌反射的趋势，但不影响神经肌肉传递。5. 唑尼沙胺的中枢作用与乙酰唑胺明显不同。即，乙酰唑胺静脉注射25 mg/kg时会显著降低脑pH值，口服100 mg/kg时会增加大鼠局部脑血流量。静脉注射50 mg/kg和口服100 mg/kg的唑尼沙胺分别对脑pH值和局部脑血流量无影响。此外，唑尼沙胺（口服100 mg/kg）会降低小鼠脑中多巴胺代谢产物DOPAC的含量，使血清素代谢产物5 - HIAA略有增加，并降低大鼠脑中多巴胺代谢产物DOPAC和HVA的含量。（摘要截于250字）
