BIIE0246: a selective and high affinity neuropeptide Y Y(2) receptor antagonist

Eur J Pharmacol. 1999 Nov 19;384(2-3):R3-5. doi: 10.1016/s0014-2999(99)00650-0.

Abstract

The in vitro biological characterisation of the first potent and selective non-peptide neuropeptide Y Y(2) receptor antagonist, (S)-N(2)-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b, e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2, 4-triazol-4-yl]ethyl]-argininamid (BIIE0246) is reported. BIIE0246 displaced [125I]neuropeptide Y with high affinity (IC(50)=3.3 nM) from the human neuropeptide Y Y(2) receptor and proved to be highly selective. BIIE0246 displayed antagonistic properties and thus represents the first selective non-peptide neuropeptide Y Y(2) receptor antagonist.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Arginine / pharmacology
  • Benzazepines / metabolism
  • Benzazepines / pharmacology*
  • Binding, Competitive / drug effects
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Humans
  • Iodine Radioisotopes
  • Male
  • Muscle Contraction / drug effects
  • Neuropeptide Y / metabolism
  • Neuropeptide Y / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Receptors, Neuropeptide Y / metabolism
  • Tumor Cells, Cultured
  • Vas Deferens / drug effects
  • Vas Deferens / physiology

Substances

  • Benzazepines
  • Iodine Radioisotopes
  • Neuropeptide Y
  • Receptors, Neuropeptide Y
  • neuropeptide Y2 receptor
  • Arginine
  • BIIE 0246