In vitro effect of N-methoxy-3-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-pyrrolidon e (E-5110), a novel nonsteroidal antiinflammatory agent, on generation of some inflammatory mediators.
Cultured rat synovial cells generate PGE2 upon stimulation with a factor derived from rate polymorphonuclear cells (Prostaglandins 27, 697, 1984). E-5110 inhibited PGE2 generation by the synovial cells. The IC50 values (microM) for inhibition of PGE2 generation were 0.026 for E-5110, 0.008 for indomethacin, 0.112 for piroxicam, 0.003 for R-830, 0.667 for BW-755C and 2.05 for benoxaprofen. Calcium ionophore A-23187-stimulated LTB4 generation by human neutrophils was inhibited by E-5110 with an IC50 value of 0.20 microM, which was similar to NDGA. The inhibition of LTB4 by E-5110 was more potent than that of R-830, BW-755C or benoxaprofen. E-5110 also inhibited superoxide generation by human neutrophils stimulated with opsonized zymosan, f-Met-Leu-Phe and phorbol myristate acetate. These results indicate that E-5110 is a potent dual inhibitor that suppresses superoxide generation.
Katayama
K
K
Eisai Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Shirota
H
H
Kobayashi
S
S
Terato
K
K
Ikuta
H
H
Yamatsu
I
I
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors; D011458:Prostaglandins E / Q000096:biosynthesis*; D011760:Pyrrolidinones / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011458:Prostaglandins E; D011760:Pyrrolidinones; C054091:E 5110; D013481:Superoxides; D007975:Leukotriene B4; D015232:Dinoprostone