Premium
Muscarinic receptor occupation and receptor activation in the guinea‐pig ileum by some acetamides related to oxotremorine
Author(s) -
Ringdahl Björn
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb16467.x
Subject(s) - oxotremorine , acetamide , muscarinic acetylcholine receptor , chemistry , stereochemistry , receptor , dissociation constant , affinities , ileum , pyrrolidine , enantiomer , pharmacology , biology , biochemistry , organic chemistry
1 The dissociation constants ( K D values) and relative efficacies of seven acetamide analogues of oxotremorine, including two enantiomeric pairs, at muscarinic receptors in the guinea‐pig isolated ileum were determined. The method used involved analysis of dose‐response data before and after fractional inactivation of receptors with propylbenzilylcholine mustard. 2 All of the compounds studied had lower affinities than oxotremorine, but some had substantially higher relative efficacies. 3 Replacement of the pyrrolidine ring of N‐methyl‐N‐(4‐pyrrolidino‐2‐butynyl)acetamide(I), the parent compound in the series, by a dimethylamino or a trimethylammonium group decreased the affinity 32 and 4.5 fold, respectively, whereas the relative efficacy increased 5.7–8.3 times. 4 There was no correlation between relative efficacies and affinities of the compounds. The structural requirements for high affinity and high efficacy appeared to be quite different.