Synthesis and pharmacology of the putative novel muscarinic agonist (S)-4-F-MePyMcN [(S)-4-(pyrrolidino)-1-methyl-2-butynyl-N-(4-fluorophenyl) carbamate oxalate]

(S)-4-F-MePyMcN [(S)-4-(pyrrolidino)-l-methyl-2-butynyl-N-(4-fluorophenyl) carbamate oxalate] has been suggested to be a selective agonist at the M-1 subtype of muscarinic receptor [Lambrecht G. et al., Life Sci. 56 (1995) 81 5-822]. We synthesized the compound and tested its selectivity for differen t muscarinic receptors with binding experiments using rat cerebral cortex s ynaptosomal membranes and cloned human mi to m5 receptors and by functional experiments on rabbit vas deferens preparations. There was little differen ce in affinity for the compound at the different cloned muscarinic receptor s (IC(50)s for displacement of H-3-N-methylscopolamine were 0.7-1.0 mu M). On rabbit vas deferens preparations, (S)-4-F-MePyMcN did reduce twitch resp onses to electrical stimulation like the known M-1 agonist McN-A-343, but u nlike McN-A-343 the compound reduced postsynaptic sensitivity to noradrenal ine, ATP and KCl. Because of these additional actions, (s)-4-F-MePyMcN may not be suitable as a tool to study M-1 muscarinic receptors selectively. (C ) Elsevier, Paris.