COMPARATIVE STUDY ON THE PHARMACOLOGICAL EFFECTS OF SOME SCOPOLIA ALKALOID DERIVATIVES

The effects of some scopolia alkaloid derivatives on M-cholinergic receptors of longitudinal muscle from guinea pig ileum were studied. Measurements of the oil/water partition coefficients and amnestie actions of these compounds were also made. Results showed that quaternization of most compounds decreased both the affinities to M-receptor and the oil/water partition coefficient. But, compounds with a hydroxyl group in the α-carbon atom of the carboxylic acid of the ester chain, such as 8610 showed potent displacement activities which were 10 and 100 times higher than those of scopolamine and N-butylscopolamine, respectively. However, the oil/water partition coefficients were lower than those of atropine and scopolamine. Twelve derivatives of the scopolia alkaloid were shown to impair memory acquisition in one trial passive avoidence responses in mice and their amnestic efficacies were 2.5～5 times lower than that of scopolamine.