一些具有胆碱乙酰转移酶抑制特性的叔烷基氨基乙酯的体内效应。

In vivo effects of some tertiary alkylaminoethyl esters with choline acetyltransferase inhibitory properties.

作者信息

Rowell P P, Chiou C Y

出版信息

Eur J Pharmacol. 1976 Nov;40(1):83-91. doi: 10.1016/0014-2999(76)90357-5.

Abstract

The tertiary nitrogen derivatives of two choline esters, chloroacetylcholine and acrylcholine, known to inhibit choline acetyltransferase (ChAc) in vitro, were tested for their effects in the whole animal, including peripheral and central cholinergic systems. These esters are N,N-dimethylaminoethyl chloroacetate (Cl-DMA) and N,N-dimethylaminoethyl acrylate (acryl-DMA). The peripheral preparations studied included a neuromuscular junction, a sympathetic ganglion and a postganglionic parasympathetic exocrine preparation. Both Cl-DMA and acryl-DMA blocked responses in these preparations when injected intravenously. The LD50 values for Cl-DMA and acryl-DMA were 640 mg/kg and 183 mg/kg, respectively. Cl-DMA and acryl-DMA were also able to inhibit brain ChAc when injected intravenously by 32% and 18.5%, respectively. The brain levels of acetylcholine (ACh) were significantly reduced by about 25% with Cl-DMA but not significantly with acryl-DMA when the animals were forced to exercise after injection. It is obvious that ChAc inhibition is not effective in decreasing ACh levels significantly under normal conditions.

摘要

已知两种胆碱酯类的叔氮衍生物，即氯乙酰胆碱和丙烯酰胆碱，在体外可抑制胆碱乙酰转移酶（ChAc），对其在包括外周和中枢胆碱能系统在内的整个动物体内的作用进行了测试。这些酯类分别是N，N - 二甲基氨基乙基氯乙酸酯（Cl - DMA）和N，N - 二甲基氨基乙基丙烯酸酯（丙烯酰 - DMA）。所研究的外周制剂包括神经肌肉接头、交感神经节和节后副交感神经外分泌制剂。静脉注射时，Cl - DMA和丙烯酰 - DMA均可阻断这些制剂中的反应。Cl - DMA和丙烯酰 - DMA的半数致死量（LD50）分别为640 mg/kg和183 mg/kg。静脉注射时，Cl - DMA和丙烯酰 - DMA也分别能抑制脑ChAc活性32%和18.5%。注射后强迫动物运动时，Cl - DMA可使脑中乙酰胆碱（ACh）水平显著降低约25%，而丙烯酰 - DMA则无显著影响。显然，在正常情况下，抑制ChAc对显著降低ACh水平并无效果。