Pharmacological studies on EB-382, a new non-steroidal antiinflammatory agents: mode of action of the analgesic effects.
The analgesic mechanism of (+/-)-2-[p-[(2-methylallyl)amino]phenyl]propionic acid (EB-382), a new non-steroidal antiinflammatory agent, was studied. EB-382 exerted a potent analgesic effect on yeast-induced hyperalgesia in rats and bradykinin-induced writhing in mice, and its potency was superior to that of ibuprofen. EB-382 had a comparatively weak inhibitory effect on the prostaglandin E2 production from arachidonic acid in sheep seminal vesicle microsomal fraction in vitro. EB-382 exhibited a dose-dependent inhibitory effect on the phospholipase A2 activity in 3T3 mouse fibroblast cells with a different mechanism from steroidal agents, although indomethacin and ibuprofen did not reveal any significant inhibition. EB-382 did not affect the bradykinin-induced contraction of isolated rat uterus. Intracisternal injection of EB-382 did not affect the acetic acid-induced writhing response in mice. From these results, it is suggested that the analgesic effect of EB-382 in inflammation is exerted through its direct peripheral action, and inhibition of prostaglandin biosynthesis via phospholipase A2, rather than cyclooxygenase.
Fujiyoshi
T
T
Iida
H
H
Murakami
M
M
Kuwashima
M
M
Uematsu
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; C027953:alminoprofen