DIFFERENTIAL ANTICHOLINERGIC ACTIVITY METABOLISM AND EXCRETION OF OPTICAL ISOMERS OF 14C-BENZETIMIDE HYDROCHLORIDE

14C-benzetimide was resolved into its optical isomers and the anticholinergic activity of these was assessed primarily by studying pupillary dilation in the rat. The anticholinergic activity of the racemic mixture was found to be exclusively due to the (+) enantiomer, but the anticholinergic efficacy was apparently not correlated with the general level of benzetimide and/or its metabolites in the tissues studied. Most radioactivity was excreted within the first 24 hr after administration of either isomer, but the rate of excretion was more rapid following administration of the (-) form. The same major metabolites (benzetamide and nor-benzetimide) were identified for both isomers, but their proportions were very different. However, oxidative N-dealkylation was a major metabolic pathway in each case. © 1969.