Vezzani A, Wu H Q, Stasi M A, Angelico P, Samanin R
Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.
Neuropharmacology. 1988 May;27(5):451-8. doi: 10.1016/0028-3908(88)90126-8.
Voltage-dependent calcium channel-blockers were studied for their ability to modulate limbic seizures induced in rats by injection of quinolinic acid and kainic acid into the hippocampus or by hippocampal kindling. Flunarizine, at 40 mg/kg (but not 20 mg/kg), reduced the total number of seizures and total time spent in seizures induced by quinolinic acid by 75%; at 60 mg/kg, both parameters were reduced more than 90%, while at 80 mg/kg seizures induced by kainic acid were not affected. Forty and 60 mg/kg of flunarizine protected hippocampal-kindled rats from fully developed convulsions (Stage 5). Nifedipine, at 20 and 40 mg/kg, was ineffective on seizures induced by both quinolinate and kainate. However, at 20 mg/kg, 57% of the kindled animals were protected from Stage 5 and total protection was achieved at 40 mg/kg. Verapamil, at 40 mg/kg, reduced by respectively, 88% and 78%, the total number of seizures and the total time spent in seizures induced by quinolinic acid, but had no effect on seizures induced by kainate and Stage 5 seizures. The results suggest that, while seizures induced by kainic acid were refractory to all voltage-dependent calcium channel blockers, binding sites affected by flunarizine and verapamil in the brain may selectively facilitate ictal activity induced by quinolinic acid. Binding sites for dihydropyridine might contribute to the increased hippocampal excitability in kindled animals. The role of calcium entry through voltage-dependent calcium channels in the occurrence of seizures in these models of limbic epilepsy is discussed.
研究了电压依赖性钙通道阻滞剂调节大鼠边缘性癫痫发作的能力，这些癫痫发作是通过向海马体注射喹啉酸和 kainic 酸或通过海马体点燃诱导产生的。氟桂利嗪，剂量为 40mg/kg（而非 20mg/kg）时，可使喹啉酸诱导的癫痫发作总数和癫痫发作总时长减少 75%；剂量为 60mg/kg 时，这两个参数减少超过 90%，而剂量为 80mg/kg 时，对 kainic 酸诱导的癫痫发作无影响。40mg/kg 和 60mg/kg 的氟桂利嗪可保护海马体点燃的大鼠免于发生完全性惊厥（5 期）。硝苯地平，剂量为 20mg/kg 和 40mg/kg 时，对喹啉酸盐和 kainate 诱导的癫痫发作均无效。然而，剂量为 20mg/kg 时，57%的点燃动物可免于进入 5 期，剂量为 40mg/kg 时可实现完全保护。维拉帕米，剂量为 40mg/kg 时，可分别使喹啉酸诱导的癫痫发作总数和癫痫发作总时长减少 88%和 78%，但对 kainate 诱导的癫痫发作和 5 期癫痫发作无影响。结果表明，虽然 kainic 酸诱导的癫痫发作对所有电压依赖性钙通道阻滞剂均有耐药性，但氟桂利嗪和维拉帕米在大脑中影响的结合位点可能选择性地促进喹啉酸诱导的发作活动。二氢吡啶的结合位点可能导致点燃动物海马体兴奋性增加。讨论了在这些边缘性癫痫模型中，通过电压依赖性钙通道进入的钙在癫痫发作发生中的作用。
