RT Journal Article
SR Electronic
T1 Comparison of the muscarinic receptor binding activity of some tertiary amines and their quaternary ammonium analogues.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 46
OP 50
VO 25
IS 1
A1 F J Ehlert
A1 D J Jenden
YR 1984
UL http://molpharm.aspetjournals.org/content/25/1/46.abstract
AB A series of tertiary amines and their N-methyl quaternary salts were examined for their ability to inhibit specific [3H]3-quinuclidinyl benzilate binding to rat brain muscarinic receptors. The more flexible tertiary amines, like dimethylaminoethyl acetate, were less potent than their respective quaternary ammonium analogues, while rigid tertiary amines, like aceclidine, were more potent than their quaternary derivatives. The competition curves of most of the compounds were adequately described by a two-site binding equation. A good correlation between pharmacological activity and the high-affinity dissociation constant was observed. The influence of pH on the competitive inhibition of [3H]3-quinuclidinyl benzilate binding by arecoline and scopolamine was also examined. The potency of these amines declined relative to that of their N-methyl derivatives as the pH increased from 8.0 to 9.0, suggesting that it is primarily the protonated form of arecoline and scopolamine which interacts with the muscarinic receptor.