T Mimaki, Y Suzuki, T Tagawa, T Karasawa, H Yabuuchi
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引用次数: 0
摘要
研究了唑尼沙胺对Sprague-Dawley大鼠脑内[3H]氟硝西泮和[3H]muscimol结合的影响。添加10(-3)M和10(-4)M唑尼沙胺后，氟硝西泮的特异性[3H]结合率分别降至64.6 +/- 5.6%(平均+/- SD, n = 5, p < 0.002)和91.9 +/- 4.0% (p < 0.005)。[3H]氟硝西泮与10(-3)M唑尼沙胺结合的Scatchard图分析显示Kd值增加，但Bmax没有变化。唑尼沙胺对GABA增强氟硝西泮特异性[3H]结合无抑制作用。在对GABA受体的影响方面，添加10(-3)M和10(-4)M唑尼沙胺后，特异性[3H]muscimol结合分别降低至27.7 +/- 10.4%(平均+/- SD, n = 4, p < 0.005)和68.3 +/- 3.7%(平均+/- SD, n = 4, p < 0.005)。由于唑尼沙胺的治疗血清水平约为10(-4)M，这些结果表明，唑尼沙胺与GABA/苯二氮卓受体离子复合物的神经药理学作用方式类似于苯妥英。
Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain.
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.
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