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

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.

• Authors: T S Saleh, R M Vianna, T B Creczynski-Pasa, S Chakravarty, B J Mavunkel, D J Kyle, J B Calixto
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 363 Issue 2-3 Pg. 179-87 (Dec 18 1998) ISSN: 0014-2999 [Print] Netherlands
• PMID: 9881588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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