ACRED P, ATKINS E M, BAINBRIDGE J G, BROWN D M, QUINTON R M, TURNER D
Br J Pharmacol Chemother. 1957 Dec;12(4):447-52. doi: 10.1111/j.1476-5381.1957.tb00163.x.
A series of esters of 1-alkyl-2-hydroxyalkylpyrrolidine and their quaternary derivatives have been shown to possess significant anti-acetylcholine activity. The benzilic acid esters were the most active, followed by xanthene-9-carboxylic acid, fluorene-9-carboxylic acid and diphenylacetic acid esters in that order. The quaternary derivatives were more active than their corresponding tertiary compounds both in vivo and in vitro. The most active compound of the series tested in vivo was (1-methylpyrrolid-2-yl)methyl benzilate methiodide and was as potent as atropine. There was a progressive decrease in anti-acetylcholine activity and a proportional increase in local anaesthetic activity as the number of carbon atoms was increased from 1 to 3 in the pyrrolidyl side-chain of the tertiary salts of the benzilic acid ester series. Likewise increasing the size of the group on the nitrogen atom led to a decrease in anti-acetylcholine activity and an increase in local anaesthetic activity. Quaternization of the tertiary salts resulted in a loss of local anaesthetic activity. Most of the compounds tested possessed some antihistamine properties, while papaverine-like activity was confined to the tertiary salts only. No significant neuromuscular blocking activity was evident.
一系列1-烷基-2-羟烷基吡咯烷酯及其季铵衍生物已被证明具有显著的抗乙酰胆碱活性。二苯乙醇酸酯活性最强，其次依次为呫吨-9-羧酸酯、芴-9-羧酸酯和二苯基乙酸酯。季铵衍生物在体内和体外均比其相应的叔化合物更具活性。该系列中在体内测试的最具活性的化合物是二苯乙醇酸甲酯甲基碘化（1-甲基吡咯烷-2-基）甲酯，其效力与阿托品相当。在二苯乙醇酸酯系列叔盐的吡咯烷基侧链中，随着碳原子数从1增加到3，抗乙酰胆碱活性逐渐降低，局部麻醉活性成比例增加。同样，增加氮原子上基团的大小会导致抗乙酰胆碱活性降低和局部麻醉活性增加。叔盐的季铵化导致局部麻醉活性丧失。大多数测试化合物具有一定的抗组胺特性，而罂粟碱样活性仅局限于叔盐。未观察到明显的神经肌肉阻滞活性。
