MUSCARINIC ACTIVITY AND RECEPTOR-BINDING OF THE ENANTIOMERS OF ACECLIDINE AND ITS METHIODIDE

Abstract

The agents (+)- and (-)-aceclidine (3-acetoxyquinuclidine), (+)- and (-)-N-methylaceclidine and oxotremorine were compared in their ability to inhibit specific 3H-labeled (.+-.)-3-quinuclidinyl benzilate binding to rat brain muscarinic receptors and to stimulate contractions of the isolated guinea pig ileum. A good correlation was observed between the high-affinity dissociation constant (KH) for binding and the muscarinic potency in the isolated ileum. The binding data for the enantiomers of aceclidine were consistent with their central and peripheral pharmacological activity in vivo. The enantiomeric potency ratios [ED50 of (-)-aceclidine/ED50 of (+)-aceclidine] for the tremorogenic, analgesic and sialogogic effects in mice agreed well with the ratio KH of (-)-aceclidine/KH of (+)-aceclidine.