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PHARMACOLOGICAL PROPERTIES OF ESTERS OF 1‐ALKYL‐2‐HYDROXYALKYLPYRROLIDINE AND THEIR QUATERNARY DERIVATIVES
Author(s) -
ACRED P.,
ATKINS E. M.,
BAINBRIDGE J. G.,
BROWN D. M.,
QUINTON R. M.,
TURNER D.
Publication year - 1957
Publication title -
british journal of pharmacology and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0366-0826
DOI - 10.1111/j.1476-5381.1957.tb00163.x
Subject(s) - methiodide , chemistry , acetylcholine , in vivo , pyrrolidinones , alkyl , tertiary amine , carboxylic acid , atropine , biological activity , hydrochloride , stereochemistry , organic chemistry , medicinal chemistry , in vitro , biochemistry , pharmacology , anesthesia , medicine , microbiology and biotechnology , biology
A series of esters of 1‐alkyl‐2‐hydroxyalkylpyrrolidine and their quaternary derivatives have been shown to possess significant anti‐acetylcboline 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.