Binding affinity and antimuscarinic activity of σ and phencyclidine receptor ligands

Abstract

The characterization of the σ receptor has been hampered by the lack of a functional bioassay system. Drugs that bind to σ receptors have been reported to inhibit carbachol-induced phosphatidylinositol turnover in rat brain; however, these drugs might directly affect muscarinic acetylcholine receptors. The purpose of the present study was to determine the affinity for muscarinic receptors and the antimuscarinic activity of σ and phencyclidine receptor ligands. All of the drugs tested inhibited the binding of [ 3H]N-methylscopolamine to guinea pig cerebral cortical membranes with K 1 values in the micromolar range and also inhibited carbachol-induced contractions in the guinea pig ileum. These results demonstrate that these compounds have substantial antimuscarinic activity which might limit the use of the inhibition of carbachol-induced phosphatidylinositol turnover as a functional assay system for studying σ ligands. Furthermore, this antimuscarinic activity must be considered when evaluating the effects of these compounds after in vivo administration.