Design and Synthesis of Piperidinyl Piperidine Analogues as Potent and Selective M2 Muscarinic Receptor Antagonists

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2247-50. doi: 10.1016/s0960-894x(00)00457-1.

Abstract

Identification of a number of highly potent M2 receptor antagonists with >100-fold selectivity against the M1 and M3 receptor subtypes is described. In the rat microdialysis assay, this series of compounds showed pronounced enhancement of brain acetylcholine release after oral administration.

MeSH terms

  • Acetylcholine / metabolism
  • Administration, Oral
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Drug Design
  • Microdialysis
  • Muscarinic Antagonists / chemical synthesis*
  • Muscarinic Antagonists / chemistry
  • Muscarinic Antagonists / pharmacology
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Rats
  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology*
  • Structure-Activity Relationship

Substances

  • Muscarinic Antagonists
  • Piperidines
  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic
  • Acetylcholine