2,3-Butanedione monoxime protects mice against the convulsant effect of picrotoxin by facilitating GABA-activated currents.
2,3-Butanedione monoxime protects mice against the convulsant effect of picrotoxin by facilitating GABA-activated currents.
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2,3-丁二酮单肟通过促进 GABA 激活电流来保护小鼠免受印防己毒素的惊厥作用。
DOI：
10.1016/0006-8993(95)00175-p
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
McArdle,JJ
中科院分区：
文献类型：
--
作者：
Brightman,T;Ye,JH;Ortiz-Jimenez,E;Flynn,EJ;Wu,WH;McArdle,JJ
虽然单独接受印防己毒素（PTX）的成年小鼠响应于阵挛性和强直-阵挛性癫痫发作，但同时注射2，3-丁二酮单肟（BDM）的小鼠的这种响应被大大抑制。例如，60%和10%的小鼠在注射（i. p.）Omg/kg PTX单独或PTX加205 mg/kg BDM。相反，BDM的非肟类似物2，3-丁二酮（BTD）没有这种抗惊厥作用。为了探讨BDM抗惊厥作用的基础，我们记录了前，中，后暴露于此肟的额叶皮层以及下丘脑腹内侧神经元的GABA激活电流（IGABA）。BDM对浓度（100 μM-40 mM）降低和较低浓度（0.01 μM-0.001 μM）增强IGABA具有双相效应; BDM的这些效应在肟洗脱后逆转。相反，BTD对IGABA没有影响。0.001 μ MBDM、10-30 μ MPTX和GABA共同作用时，毒素对IGABA的抑制作用明显减弱。这些数据表明，肟的抗惊厥作用涉及促进GABA的抑制作用。
While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (IGABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on concentrations (100 μM-40 mM) decreased and lower concentrations (0.01 μM–0.001 μM) potentiated IGABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect on IGABA. Finally, when 0.001 μM BDM, 10–30 μM PTX and GABA were co-applied the inhibitory effect of the toxin on IGABAwas markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA.