Formation of a highly stable complex between BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-a] diazepine-1,4] and the platelet-activating factor receptor in rabbit platelet membranes

Biochem Pharmacol. 1996 Jan 26;51(2):193-6. doi: 10.1016/0006-2952(95)02158-2.

Abstract

BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-alpha] diazepine-1,4], a novel platelet-activating factor (PAF) receptor antagonist with a hetrazepine structure, decreased the maximal number of binding sites (Bmax) of [3H]PAF in rabbit platelet membranes without altering its dissociation constant. Platelet aggregation induced by 1 microM PAF was prevented by preincubation with 1 microM BN 50730. The washing of the platelets preincubated with BN 50730 failed to revert its inhibitory effects. We conclude that BN 50730 acts as a non-competitive antagonist of the PAF receptor, due to the formation of a highly stable drug-receptor complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azepines / chemistry
  • Azepines / pharmacology*
  • Binding Sites
  • Blood Platelets / metabolism*
  • Cell Membrane / metabolism
  • Platelet Activating Factor / antagonists & inhibitors
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Membrane Glycoproteins / antagonists & inhibitors*
  • Platelet Membrane Glycoproteins / chemistry
  • Rabbits
  • Receptors, Cell Surface*
  • Receptors, G-Protein-Coupled*
  • Thienopyridines
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Azepines
  • Platelet Activating Factor
  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Thienopyridines
  • Triazoles
  • platelet activating factor receptor
  • BN 50730