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  • Title: In vivo effects of some tertiary alkylaminoethyl esters with choline acetyltransferase inhibitory properties.
    Author: Rowell PP, Chiou CY.
    Journal: Eur J Pharmacol; 1976 Nov; 40(1):83-91. PubMed ID: 186280.
    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.
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