Inhibition of prostaglandin generation in the rabbit brain in-vivo by AD-1590, a non-steroidal antiinflammatory agent with potent antipyretic activity

Abstract

Abstract The inhibition of prostaglandin generation by AD-1590 was investigated in the rabbit brain in-vivo. AD-1590 (0ṁ4 mg kg−1 i.v.) markedly prevented both the increases in body temperature and PGE2 level in cerebrospinal fluid (CSF) caused by i.v. injection of lipopolysaccharide. On the other hand, 2,4-dinitrophenol (20 mg kg−1 i.v.)-induced hyperthermia, which was not affected by AD-1590, was not accompanied by an increase in PGE2 level in CSF. When injected intracerebroventricularly, AD-1590 dose-dependently inhibited the hyperthermia caused by arachidonic acid given by the same route; its ED50 was 1ṁ6 μg compared with about 35 μg for indomethacin. From these results, it is suggested that AD-1590 is more active than indomethacin in suppressing prostaglandin synthetase in rabbit brain.