Oral anti-inflammatory action of NPC 18884, a novel bradykinin B2 receptor antagonist.
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.
Saleh
T S
TS
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Vianna
R M
RM
Creczynski-Pasa
T B
TB
Chakravarty
S
S
Mavunkel
B J
BJ
Kyle
D J
DJ
Calixto
J B
JB
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives; D065168:Bradykinin Receptor Antagonists; D002351:Carrageenan; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D006632:Histamine; D008297:Male; D051379:Mice; D010998:Pleurisy / Q000139:chemically induced / Q000517:prevention & control*; D043782:Receptor, Bradykinin B2; D013373:Substance P
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D004151:Dipeptides; C117759:NPC 18884; D043782:Receptor, Bradykinin B2; C024626:bradykinin, des-Arg(9)-; D013373:Substance P; D006632:Histamine; D002351:Carrageenan; D001920:Bradykinin