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1,3-oxathiolane muscarinic ligands modified at the cationic head.

In order to develop compounds which may be useful in the treatment of memory and cognitive disorders we have synthesized and tested some 1,3-oxathiolane derivatives bearing an amidine function instead of the classical ammonium head, with the aim of improving brain penetration. The compounds were tested on peripheral and central models of muscarinic receptors. The results show that, unlike for other series of muscarinic ligands, this modification results in the reduced potency of antagonists, shifts the activity of agonists toward weak antagonism and does not introduce any noteworthy subtype selectivity.