Mimaki T, Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H
Department of Pediatrics, Osaka University Medical School, Japan.
Med J Osaka Univ. 1990 Mar;39(1-4):13-7.
The effects of zonisamide on [3H]flunitrazepam binding and [3H]muscimol binding were studied in Sprague-Dawley rat brain. Specific [3H]flunitrazepam bound was decreased to 64.6 +/- 5.6% (mean +/- SD, n = 5, p < 0.002) and 91.9 +/- 4.0% (p < 0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively. Scatchard plot analysis of [3H]flunitrazepam binding with 10(-3) M of zonisamide revealed an increased Kd value with no change in Bmax. No inhibitory effect of zonisamide was seen on the enhancement of specific [3H]flunitrazepam binding by GABA. As for the effects on GABA receptors, specific [3H]muscimol bound was decreased to 27.7 +/- 10.4% (mean +/- SD, n = 4, p < 0.005) and 68.3 +/- 3.7% (mean +/- SD, n = 4, p < 0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively. Since therapeutic serum level of zonisamide are around 10(-4) M, these results suggest that zonisamide neuropharmacologically interacts with the GABA/benzodiazepine receptor ionophore complex in a manner similar to phenytoin.
在斯普拉格-道利大鼠脑内研究了唑尼沙胺对[³H]氟硝西泮结合及[³H]蝇蕈醇结合的影响。加入10⁻³M和10⁻⁴M唑尼沙胺后，特异性结合的[³H]氟硝西泮分别降至64.6±5.6%（平均值±标准差，n = 5，p < 0.002）和91.9±4.0%（p < 0.005）。用10⁻³M唑尼沙胺对[³H]氟硝西泮结合进行Scatchard图分析显示，解离常数（Kd）值增加，最大结合量（Bmax）无变化。未观察到唑尼沙胺对γ-氨基丁酸（GABA）增强特异性[³H]氟硝西泮结合有抑制作用。至于对GABA受体的影响，加入10⁻³M和10⁻⁴M唑尼沙胺后，特异性结合的[³H]蝇蕈醇分别降至27.7±10.4%（平均值±标准差，n = 4，p < 0.005）和68.3±3.7%（平均值±标准差，n = 4，p < 0.005）。由于唑尼沙胺的治疗血清水平约为10⁻⁴M，这些结果表明唑尼沙胺在神经药理学上与GABA/苯二氮䓬受体离子通道复合物相互作用，其方式类似于苯妥英。
