SYNTHESIS AND PHARMACOLOGICAL INVESTIGATION OF CHOLINERGIC LIGANDS STRUCTURALLY RELATED TO MUSCARONE

Five new analogs of muscarone were synthesized in order to evaluate the influence of the carbonyl group on muscarinic activity. We chose to introduce structural variations at the C-2 and C-3 positions of the tetrahydrofuran ring. The muscarinic activity was evaluated in vitro on guinea pig atria and ileum as well as on rat jejunum and urinary bladder. All the new derivatives are less potent than muscarone and three of them displayed a potency very close to that previously reported for muscarine. The tissue selectivity observed for the 3-methylene derivative which is eight times more potent on guinea pig ileum than atria is worth noting. The present data show the lack of a simple relationship between the polarity of the group located in the 3-position of the ring and the muscarinic activity.