1. Succinimide derivatives can be either convulsant (tetramethylsuccinimide (TMS)), or anticonvulsant (ethosuximide (ES); alpha-methyl-alpha-phenylsuccinimide (MPS)). ES, an anticonvulsant succinimide, has previously been shown to block calcium currents of thalamic neurones, while the convulsant succinimide TMS blocks gamma-aminobutyric acid (GABA) responses in a similar fashion to the convulsant pentylenetetrazol (PTZ). 2. Using voltage-clamp techniques, we analysed the effects of the anticonvulsant succinimides ES and MPS and the convulsants TMS and PTZ on calcium currents of acutely isolated thalamic relay neurones of the rat. 3. MPS and ES reduced low-threshold calcium current (LTCC) in a voltage-dependent manner, without affecting steady-state inactivation. MPS was less potent than ES (IC50 of 1100 vs 200 microM) but greater in efficacy (100% maximal reduction vs 40% for ES). 4. PTZ had no effect on calcium currents, and TMS only reduced LTCC at very high concentrations, and did not occlude MPS effects when applied concurrently. 5. These results, which demonstrate that anticonvulsant, but not convulsant, succinimides block LTCC, provide additional support for the hypothesis that LTCC reduction is a mechanism of action of the anticonvulsant succinimides related to their effects in petit mal epilepsy.

译文

1。琥珀酰亚胺衍生物可以是惊厥剂 (四甲基琥珀酰亚胺 (TMS)),也可以是抗惊厥剂 (ethosuximide (ES); Α-甲基-α-苯基琥珀酰亚胺 (MPS))。ES是一种抗惊厥药琥珀酰亚胺,以前已被证明可以阻断丘脑神经元的钙电流,而惊厥药琥珀酰亚胺TMS则以与惊厥药戊四氮 (PTZ) 相似的方式阻断 γ-氨基丁酸 (GABA) 反应。2.使用电压钳技术,我们分析了抗惊厥药琥珀酰亚胺ES和MPS以及惊厥药TMS和PTZ对大鼠急性分离的丘脑中继神经元钙电流的影响。3. MPS和ES以电压依赖性方式降低了低阈值钙电流 (LTCC),而不影响稳态失活。MPS的效力低于ES (1100的IC50与200的microM),但效力更高 (100% 的最大降低与ES的40%)。4. PTZ对钙电流没有影响,TMS仅在非常高的浓度下降低LTCC,同时使用时不会抑制MPS效应。5.这些结果表明抗惊厥药而非惊厥药琥珀酰亚胺阻断LTCC,为LTCC减少是抗惊厥药琥珀酰亚胺的作用机制与它们在小癫痫中的作用有关的假说提供了额外的支持。

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