Accession Number : AD0765006

Title :   Antagonism at the Cholinergic Receptor of Denervated Diaphragm by Monoquaternary and Bisquaternary Nitrogen Compounds,

Corporate Author : DEFENCE STANDARDS LABS MARIBYRNONG (AUSTRALIA)

Personal Author(s) : Freeman,Shirley E. ; Turner,R. J.

Report Date : 10 AUG 1972

Pagination or Media Count : 10

Abstract : A study was made of the actions of agonists and antagonists at the cholinergic receptor of denervated rat diaphragm. The antagonists studied were tetraethylammonium, 3-hydroxyphenyltriethylammonium, 3-hydroxyphenyldiethylmethylammonium, ambenonium and methoxyambenonium. Acetylcholine, carbachol and tetramethylammonium were used as agonists. The effects of the drugs on agonist-induced isometric contractions and depolarizations were studied. Logarithmic plots of (dose ratio -- 1) against antagonist concentration yielded regressions with slopes greater than unity when monoquaternary antagonists were used, and less than unity when bisquaternary compounds were used. In every instance acetylcholine required higher levels of antagonist to produce dose-ratios comparable to carbachol or tetramethylammonium. This effect is unlikely to be due to cholinesterase inhibition. It is suggested that there is a second anionic site in the vicinity of the receptor, which binds cholinergic agonists and antagonists, and which has regulatory or allosteric effects on the receptor. (Author)

Descriptors :   (*PARASYMPATHOLYTIC AGENTS, PHARMACOLOGY), (*NITROGEN COMPOUNDS, PARASYMPATHOLYTIC AGENTS), (*PARASYMPATHOMIMETIC AGENTS, PHARMACOLOGY), ACETYLCHOLINE, AUTONOMIC AGENTS

Subject Categories : Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE