Mechanism of anti-inflammatory action of etodolac.
The effect of etodolac (CAS 41340-25-4) on the inflammatory reactions induced by histamine and bradykinin was compared with that of indomethacin and other nonsteroidal anti-inflammatory drugs. Etodolac (50 mg/kg p.o.), indomethacin (20 mg/kg p.o.), diclofenac Na (20 mg/kg p.o.) and acetylsalicylic acid (200 mg/kg p.o.) had no effect on the increase of vascular permeability induced by histamine or bradykinin and on passive cutaneous anaphylaxis in rats. Etodolac (5, 10 and 20 mg/kg p.o.) suppressed concanavalin A-induced paw edema in rats. Etodolac (10 mg/kg p.o.) and bromelain (10 mg/kg i.v.) significantly suppressed the heat-induced elevation of bradykinin in perfusates of rat paws, but indomethacin (20 mg/kg p.o.) and diclofenac Na (20 mg/kg p.o.) did not. Etodolac inhibited bradykinin-forming enzyme activity in a concentration-dependent manner (IC50 = 1.5 x 10[-4) mol/l). These results suggest that etodolac is a unique nonsteroidal anti-inflammatory drug which can inhibit bradykinin formation, unlike indomethacin or diclofenac Na.
Inoue
K
K
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Motonaga
A
A
Nishimura
T
T
Yokota
M
M
Miki
N
N
Fujisawa
H
H
Ueda
F
F
Shibata
Y
Y
Kimura
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001920:Bradykinin / Q000096:biosynthesis / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D003208:Concanavalin A; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D017308:Etodolac; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D007210:Indoleacetic Acids / Q000494:pharmacology*; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D003208:Concanavalin A; D017308:Etodolac; D006632:Histamine; D001920:Bradykinin