Tissue selective localization of oral cimetropium bromide to muscarinic receptors in colonic smooth muscle

The time-related distribution and muscarinic receptor binding of orally administered cimetropium, a quaternary ammonium antimuscarinic drug, in longitudinal smooth muscle of intestinal segments and other bodily tissues of the rat was investigated in parallel with atropine in an in-vivo binding study combined with autoradiograpic imaging. Unlike the binding of the quaternary drug in duodenum, jejunum and ileum, which decreased with time, the binding of the drug to colonic smooth muscle increased with time over a 15-h period. Binding was absent in the right atrium and minor and temporary in submandibular glands. The tissue distribution of (3H)cimetropium 24 h after oral administration mirrored the binding data. Micro-autoradiographic imaging performed 24 h after oral administration of (14C)cimetropium showed silver grains to be distributed in highest density in colonic tissues, i.e. the smooth muscles, blood vessels (mainly venulesj and the deep mucosal glands; and in hepatocytes. Negligible grain densities were seen in heart, exocrine glands and other bodily tissues. The results indicate that oral cimetropium, differently from atropine, accumulates selectively in colon–and binds specifically there to muscarinic receptors in smooth muscle–by a mechanism more reflective of transit along the enterai tract, and local uptake and elimination, than absorption in the upper gastrointestinal region.