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新型三肽类神经降压素类似物双轻肽选择性影响伏隔核和下丘脑的多巴胺代谢

[The new tripeptoid neurotensin analog dilept selectively affects dopamine turnover in nucleus accumbens and hypothalamus].

作者信息

Retiunskaia M V, Kudrin V S, Klodt P M, Us K S, Gudasheva T A, Ostrovskaia R U

出版信息

Eksp Klin Farmakol. 2005 Nov-Dec;68(6):15-8.

Abstract

The effects of dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) - a new peptidomimetic of neurotensine - on the level of monoamines and their main metabolites in four functionally important brain structures has been studied upon single and subchronic administration in intact rats and in those pretreated with the NMDA receptor blocker ketamine. Repeated administration of dilept favors the accumulation of DOPAC and accelerates the dopamine (DA) turnover in nucleus accumbens, as manifested by an increase in the DOPAC/DA ratio. The opposite effect (decrease in the DOPAC/DA ratio) was observed in the hypothalamus, where the subchronic treatment with dilept completely inhibited the activating action of ketamine on the DA turnover. The selective influence of dilept on the dopaminergic system activity in nucleus accumbens (but not in striatum), together with the previously obtained behavioral data, suggest that dilept is a new atypical neuroleptic producing no extrapyramidal side effects.

摘要

研究了新型神经降压素拟肽二肽(N-己酰基-L-脯氨酰-L-酪氨酸甲酯)单次和亚慢性给药对完整大鼠以及用NMDA受体阻滞剂氯胺酮预处理的大鼠四个功能重要脑区单胺及其主要代谢产物水平的影响。重复给药二肽有利于3,4-二羟基苯乙酸(DOPAC)的积累,并加速伏隔核中多巴胺(DA)的周转,表现为DOPAC/DA比值增加。在下丘脑中观察到相反的效果(DOPAC/DA比值降低),其中二肽亚慢性治疗完全抑制了氯胺酮对DA周转的激活作用。二肽对伏隔核(而非纹状体)多巴胺能系统活性的选择性影响,以及先前获得的行为学数据表明,二肽是一种新型非典型抗精神病药物,不产生锥体外系副作用。

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