The affinity of some acetylenic analogues of 4‐DAMP methobromide for muscarinic receptors in guinea‐pig ileum and atria

Abstract

The replacement of 4‐hydroxy‐N‐methyl piperidine (HO‐NMe) in 4‐diphenylacetoxy‐N‐methyl piperidine (4‐DAMP) metho‐bromide by 4‐hydroxy‐but‐2‐ynylamines (HOCH 2 CĈH 2 NR 2 ) reduces the affinity for muscarine‐sensitive acetylcholine receptors in guinea‐pig ileum and atria. It does not abolish selectivity. The tertiary amines are more active and more selective than the corresponding quaternary salts. Analogous derivatives of 4‐hydroxy‐but‐2‐ynylamines which lack the ester group (i.e. substituted 4‐hydroxymethyl‐propynyl amines) are less active and less selective. The quaternary compounds are more active than the tertiary bases. The diphenylcarbamyl ester of 4‐hydroxy‐N‐methylpiperidine methobromide has less than one‐thousandth of the activity of the diphenylacetyl ester (4‐DAMP methobromide) and is not selective. Although 4‐diphenylacetoxy‐butynyl dimethylamine is only about one‐hundredth as active as 4‐DAMP methobromide it appears to have comparable selectivity. It is an interesting compound because it is a tertiary amine and should cross membranes.