title: M1 muscarinic antagonists interact with sigma recognition sites.
abstract: The M1-selective muscarinic antagonists aprophen, caramiphen, carbetapentane, 2-DAEX, dicyclomine, hexahydrosiladifenidol, iodocaramiphen, nitrocaramiphen, oxybutynin and trihexyphenidyl potently inhibited binding to sigma sites in brain. Both basic ester and non-ester structural type compounds which exhibit affinity for the muscarinic receptor also demonstrated affinity for the sigma site, while the classical antimuscarinic agents atropine and QNB, and the tricyclic pirenzepine, were ineffective in binding to this site. We also observed a significant correlation between the Ki values for sigma compounds to inhibit [3H]pirenzepine binding and their IC50 values to inhibit carbachol-stimulated phosphoinositide turnover. These observations may aid in elucidating the relationship of sigma binding to inhibition of phosphoinositide turnover stimulated by cholinergic agonists.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0540.
authors.forename: R L
authors.initials: RL
authors.lastname: Hudkins
authors.forename: D L
authors.initials: DL
authors.lastname: DeHaven-Hudkins
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D018727:Muscarinic Antagonists; D010276:Parasympatholytics / Q000378:metabolism* / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017480:Receptors, sigma
chemical_list: D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010716:Phosphatidylinositols; D011957:Receptors, Opioid; D017480:Receptors, sigma