Oral anti-inflammatory action of NPC 18884, a novel bradykinin B2 receptor antagonist

Eur J Pharmacol. 1998 Dec 18;363(2-3):179-87. doi: 10.1016/s0014-2999(98)00778-x.

Abstract

This study describes the anti-inflammatory actions of NPC 18884, a non-peptide bradykinin B2 receptor antagonist in bradykinin and carrageenan-induced inflammation in the mouse model of pleurisy. The selectivity of NPC 18884 was assessed in the pleurisy caused by histamine, substance P and des-Arg9-bradykinin. NPC 18884 given intraperitoneally or orally inhibited bradykinin-induced leukocytes influx (ID50 value of 63 nmol/kg and 141 nmol/kg, respectively). The NPC 18884 also inhibited the exudation induced by bradykinin (P < 0.05). NPC 18884 given either intraperitoneally or orally caused dose-dependent inhibition of the exudation and total and differential cell content caused by intrapleural injection of carrageenan (1%, assessed 4 h after), with mean ID50, values of 132 and 295 nmol/kg, respectively. The NPC 18884 actions installs rapidly (0.5 h), lasted for up to 4 h and were selective for the bradykinin B2 receptors; at similar doses it had no significant effect against the inflammatory responses induced by des-Arg9-bradykinin, histamine or substance P. These results indicate that the novel non-peptide bradykinin B2 receptor antagonist, NPC 18884, exhibited selective intraperitoneal and oral anti-inflammatory properties when assessed in the inflammatory reaction induced by bradykinin and carrageenan in the mice model of pleurisy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Bradykinin / analogs & derivatives
  • Bradykinin Receptor Antagonists*
  • Carrageenan
  • Dipeptides / pharmacology
  • Dipeptides / therapeutic use*
  • Disease Models, Animal
  • Drug Interactions
  • Female
  • Histamine
  • Male
  • Mice
  • Pleurisy / chemically induced
  • Pleurisy / prevention & control*
  • Receptor, Bradykinin B2
  • Substance P

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Bradykinin Receptor Antagonists
  • Dipeptides
  • NPC 18884
  • Receptor, Bradykinin B2
  • bradykinin, des-Arg(9)-
  • Substance P
  • Histamine
  • Carrageenan
  • Bradykinin