Comparison of the Antimuscarinic Action of p- Fluorohexahydrosiladifenidol in Ileal and Tracheal Smooth Muscle

We investigated the ability of the muscarinic antagonist p-fluorohexahydrosiladifenidol to inhibit muscarinic agonist-in-duced contractions and phosphoinositide hydrolysis in the guinea pig ileum and trachea. This antagonist displayed higher potency at blocking oxotremorine-M-induced contractions of the ileum compared with those of the trachea. When estimated using a simple model for competitive antagonism, the observed dissociation constant of p-fluorohexahydrosiladifenidol exhib-ited approximately 12-fold higher potency in the ileum com-pared with the trachea. We also investigated the ability of p-fluorohexahydrosiladifenidol to affect the inhibition of con-traction caused by the known competitive muscarinic antago-nist atropine. Using resultant analysis to analyze this interac-tion, we found that the true dissociation constant o