Anti-Inflammatory Action of Orally Active 5-Lipoxygenase Inhibitor TMK688

Abstract

A topical application of 12-0-tetradecanoylphorbol-13-acetate (TPA) to mouse ear surface induces nonallergic inflammation, i.e. ear edema. Oral administration of 3-30 mg/kg of l-{[5’-(3”-methoxy-4”-ethoxycarbonyloxyphenyl)-2’,4’-pentadienoyl]aminoethyl}-4-diphenylmethoxypiperidine (TMK 688), a potent 5-lipoxygenase inhibitor with antihistamine activity, inhibited TPA-induced ear edema in a dose-dependent manner. TMK688 inhibited not only 5-lipoxygenase activity but also epidermal cyclooxygenase activity. 1 – {[ 5 ‘ (3 “ methoxy – 4”-hy droxyphenyl) – 2’, 4’- pentadienoyl] -aminoethyl}-4-diphenylmethoxypiperidine (TMK777), an active metabolite of TMK688, had more potent 5-lipoxygenase inhibitory activity but less potent cyclooxygenase inhibitory activity than TMK688. Oral administration of TMK688 (30 mg/kg) markedly inhibited TPA-stimulated LTB₄ formation in mouse skin but TPA-stimulated PGE₂ formation only slightly. Our experimental results suggest that both cyclooxygenase inhibitory activity and antihistamine activity of TMK688 are not essential to its anti-inflammatory action. The anti-inflammatory effect of orally administered TMK688 is due most probably to the anti-5-lipoxygenase activity of TMK688 and its active metabolite TMK777.

Further studies on anti-inflammatory activity of phycocyanin in some animal models of inflammation

“…Oedema was induced in the right ear of mice by topical application of 4 g/ear of TPA in acetone [8]. The left ear (control) received vehicle (acetone, 20 L).…”

Effects of Phycocyanin Extract on Prostaglandin E2 Levels in Mouse Ear Inflammation Test

“…Oedema was induced in the right ear of mice by topical application of 4 µg/ear of TPA in acetone [8]. The left ear (control) received vehicle (acetone, 20 µl).…”

Preview of Potential Therapeutic Applications of Leukotriene B4 Inhibitors in Dermatology

“…This suggested that neither cyclooxygenase inhibition nor antihistaminic activity were essential to the antiinflammatory action of linetastine. The antiinflammatory effect of oral linetastine is probably due to 5-LO inhibition [54]. Jiang et al [23] found oral administration of linetastine inhibited both TPA-promoted and non-TPApromoted skin tumor formation in 7,12-dimethylbenz[a]anthracene-initiated CD-1 mice.…”