Pharmacological properties of the new non-steroidal anti-inflammatory agent etodolac.
The anti-inflammatory, analgesic, antipyretic and ulcerogenic activities of etodolac (CAS 41340-25-4), a new nonsteroidal anti-inflammatory agent, were compared with those of indometacin and other anti-inflammatory drugs in experimental animals. Etodolac had a remarkable anti-inflammatory effect in various experimental models: ultraviolet erythema, carrageenin-induced edema and swelling of adjuvant arthritis. In these models, the effective dose of etodolac was several fold that of indometacin. Etodolac inhibited prostaglandin E2 formation in a concentration-dependent manner, and its inhibitory potency was about 1/5 of that of indometacin. Etodolac also caused marked inhibition of granuloma formation and leucocyte functions such as chemotaxis, lysosomal enzyme release and active oxygen generation. These effects of etodolac were observed at similar doses of indometacin. Etodolac suppressed inflammatory pain but not non-inflammatory pain, and had an antipyretic effect but did not lower normal rectal temperature. Etodolac had no effect on delayed hypersensitivity reactions and was much less ulcerogenic than indometacin. These results indicate that etodolac is a low ulcerogenic anti-inflammatory agent with suppressing activities on leucocyte functions to the same extent as indometacin and prostaglandin biosynthesis.
Inoue
K
K
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Fujisawa
H
H
Sasaki
Y
Y
Nishimura
T
T
Nishimura
I
I
Inoue
Y
Y
Yokota
M
M
Masuda
T
T
Ueda
F
F
Shibata
Y
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D002358:Cartilage, Articular / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004890:Erythema / Q000188:drug therapy; D017308:Etodolac; D005753:Gastric Mucosa / Q000187:drug effects; D006099:Granuloma / Q000188:drug therapy; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007210:Indoleacetic Acids / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011453:Prostaglandins / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D011453:Prostaglandins; D013481:Superoxides; D017308:Etodolac