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[卡比定立体异构体的神经化学特征比较研究]

[A comparative study of the neurochemical profiles of carbidine stereoisomers].

作者信息

Gaĭnetdinov R R, Miroshnichenko I I, Kudrin V S, Bogdanov M B, Pogorelov V M, Budygin E A, Kovalev G I, Raevskiĭ K S

出版信息

Eksp Klin Farmakol. 1993 Jan-Feb;56(1):24-7.

PMID:8100728
Abstract

The effects of cis- and trans-isomers of atypical neuroleptic carbidine on the synthesis of dopamine and its autoreceptor regulation in the striatum and nucleus accumbens of rats were examined by blocking decarboxylase of L-aromatic amino acids and interrupting the nerve impulse flow in the dopaminergic neurons. The striatal release and metabolism of dopamine were studied in vitro by employing K(+)-stimulated efflux from isolated striata and in vivo by the microdialysis in freely moving rats. Carbidine trans-isomer, unlike its cis-isomer, was shown to enhance the biosynthesis of dopamine via blockade of presynaptic autoreceptors presumably located on the dopaminergic terminals. The trans-isomer was found to be much more potent by affecting the neurochemical parameters of dopaminergic neurotransmission, which are essential for the drug to produce its antipsychotic effect.

摘要

通过阻断L-芳香族氨基酸脱羧酶并中断多巴胺能神经元中的神经冲动流,研究了非典型抗精神病药物卡比定的顺式和反式异构体对大鼠纹状体和伏隔核中多巴胺合成及其自身受体调节的影响。通过采用K(+)刺激离体纹状体的外流,在体外研究了多巴胺在纹状体中的释放和代谢,并通过对自由活动大鼠进行微透析在体内进行了研究。结果表明,卡比定反式异构体与其顺式异构体不同,它可能通过阻断位于多巴胺能终末的突触前自身受体来增强多巴胺的生物合成。发现反式异构体通过影响多巴胺能神经传递的神经化学参数,其效力要强得多,而这些参数对于该药物产生抗精神病作用至关重要。

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