Derivatives of the Muscarinic Agent N-Methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide

Article abstract of DOI:10.1021/jm00398a015

A series of tertiary and quaternary analogues (acyclic imides, sulfonimides, N-acetyl sulfonamides, and trifluoroacetamides) of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5, 35) was synthesized.The compounds were found to be muscarinic agonists, partial agonists, or antagonists in the isolated guinea pig ileum.Replacement of the acetyl group or the N-methyl group of 35 and its analogues by a methanesulfonyl group abolished efficacy and decreased affinity at ileal muscarinic receptors.Trifluoroacetamide analogues of 35 also had lower affinity and efficacy than 35.Substitution of an acetyl group for the N-methyl group in compounds related to 35 decreased efficacy, but had no appreciable effect on affinity.Most of the tertiary amines showed central antimuscarinic activity as they antagonized oxotremorine-induced tremors in mice.