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

J Med Chem. 1988 Mar;31(3):577-82. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetamides
  • Animals
  • Fluoroacetates
  • Guinea Pigs
  • Ileum / drug effects
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Mice
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Parasympathomimetics / chemical synthesis*
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology
  • Receptors, Muscarinic / metabolism
  • Structure-Activity Relationship


  • Acetamides
  • Fluoroacetates
  • Parasympathomimetics
  • Pyrrolidines
  • Receptors, Muscarinic
  • trifluoroacetamide
  • N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide