DEVELOPMENT OF DRUG CROSS-TOLERANCE IN PATIENTS TREATED CHRONICALLY WITH ATROPINE

Studies were carried out on the quantitative inhibitory effect of a quaternary parasympatholytic compound (Gastrixone: 8-methyl-tropinium-bromide-xanthene-9-carboxilate) upon the basal and reflex parotid secretion in patients treated chronically with atropine before, during (2-4 weeks) treatment and 3-6 days after cessation of treatment. A significant decrease in the inhibitory effect of Gastrixone was observed during the course of treatment. This was shown to be a reversible process since the original effect returned 3-6 days after the end of atropine treatment. No alterations in absorption, metabolism and excretion of Gastrixone were found during the atropine treatment. These results suggest the development of drug cross-tolerance to Gastrixone during the course of atropine treatment. The hypothesis is put forward, based on experiments on cholinesterase activity, that the site of the drug cross-tolerance phenomenon is at the receptor level, the alteration of cholinergic receptor structure being induced by prolonged atropine treatment. © 1969.