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氯美噻唑对大鼠脑内单单位活动的影响；与抑制性和兴奋性神经递质的相互作用。

The effects of chlormethiazole on single unit activity in rat brain; interactions with inhibitory and excitatory neurotransmitters.

作者信息

Gent J P, Wacey T A

出版信息

Br J Pharmacol. 1983 Nov;80(3):439-44. doi: 10.1111/j.1476-5381.1983.tb10713.x.

DOI:10.1111/j.1476-5381.1983.tb10713.x

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2044992/

Abstract

Extracellular recordings were made of single unit activity in the brainstem of urethane anaesthetized rats. Drugs were applied by microiontophoresis from multibarrelled micropipettes or administered intraperitoneally. Chlormethiazole (CMZ) caused a decrease in spontaneous firing rate when applied with high currents (greater than 40 nA). When applied with lower currents CMZ did not cause changes in firing rate, but enhanced the inhibitory effects of gamma-aminobutyric acid (GABA), muscimol and glycine in a dose-dependent manner. The inhibitory actions of acetylcholine were not affected. Excitatory responses to glutamate and acetylcholine were unaffected by applications of CMZ which caused potentiation of GABA, muscimol and glycine. When applied at higher currents CMZ caused a decrease in the response to glutamate. Intraperitoneal administration of CMZ (50-600 mumol kg-1) also enhanced responses to microiontophoretically applied GABA, muscimol and glycine. These results are compared with those reported for other anticonvulsant drugs and possible mechanisms of action of CMZ are discussed.

摘要

在乌拉坦麻醉的大鼠脑干中进行细胞外记录，以记录单个神经元的活动。药物通过多管微量移液器进行微量离子导入或腹腔注射给药。当以高电流（大于40 nA）应用时，氯美噻唑（CMZ）会导致自发放电率降低。当以较低电流应用时，CMZ不会引起放电率的变化，但会以剂量依赖的方式增强γ-氨基丁酸（GABA）、蝇蕈醇和甘氨酸的抑制作用。乙酰胆碱的抑制作用不受影响。对谷氨酸和乙酰胆碱的兴奋性反应不受导致GABA、蝇蕈醇和甘氨酸增强的CMZ应用的影响。当以较高电流应用时，CMZ会导致对谷氨酸的反应降低。腹腔注射CMZ（50 - 600 μmol kg-1）也会增强对微量离子导入应用的GABA、蝇蕈醇和甘氨酸的反应。将这些结果与其他抗惊厥药物的报道结果进行了比较，并讨论了CMZ可能的作用机制。