Abstract
The mode of anti-inflammatory action of 2-(8-methyl-l0, 11-dihydro-11-oxodibenz[b, f]-oxepin-2-yl)propionic acid (AD-1590), a new non-steroidal anti-inflammatory drug, was investigated mainly in in vitro models. Inhibitory potency (lC50=0.056μM) of AD-1590 for prostaglandin E2 biosynthesis by rat peritoneal macrophages was about 2.2 times that of indomethacin. AD-1590 showed inhibitory activity against carboxymethyl cellulose-induced leukocyte emigration and protein exudation at a local dose of 1.2 mg/pouch in rats and its maximal activity tended to be superior to that of indomethacin. AD-1590 (100μg/ml) inhibited uptake of 3H-thymidine into rat thymocytes in the presence of phytohemagglutinin-P, but not in the absence of it; indomethacin inhibited both the uptakes. Inhibitory potencies of AD-1590 for hypotonic-hyperthermic lysis of rat erythrocytes (IC50=12.0μM) and heat-denaturation of bovine serum albumin (IC50=25.6μM) were about0.5 times that of indomethacin, and about 2.2 times that of diclofenac sodium, respectively. These findings indicated that AD-1590 has inhibitory activities on prostaglandin biosynthesis, leukocyte emigration, heat-denaturation of albumin and lymphocyte transformation, and membrane stabilizing action, but anti-inflammatory drugs tested affect these responses at different degrees. From these results, it is suggested that AD-1590 shows anti-inflammatory activity through the mechanisms generally similar to indomethacin, while it has more potent inhibitory activity for prostaglandin biosynthesis than indomethacin.
