The analgesic effect profile of FR122047, a selective cyclooxygenase-1 inhibitor, in chemical nociceptive models

The pharmacological profile of the analgesic agent, 1-[(4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl]-4-methylpiperazine hydrochloride (FR122047), was investigated. In recombinant human cyclooxygenase enzyme assays, the inhibition of prostaglandin E-2 formation by FR122047 was 2300 times more selective for cyclooxygenase-1 than cyclooxygenase-2. Oral administration of FR122047 (3.2-100 mg/kg) dose dependently reduced the phase ? response (10-60 min) of the formalin test in rats. This effect was 3 times less potent than that of indomethacin. FR112047 (1-32 mg/kg; p.o.) showed a dose-dependent analgesic effect against the acetic acid-induced writhing response in mice. Furthermore, FR122047 (0.01-10 mg/kg, p.o.) inhibited the increase in 6-keto prostaglandin F-1 alpha level in acetic acid-injected mouse peritoneal cavity. However, a selective cyclooxygenase-2 inhibitor, NS-398, had no effect in these cyclooxygenase-l sensitive pain models. These results suggest that FR122047, a selective cyclooxygenase-l inhibitor, shows an analgesic effect in chemical nociceptive models and may be a useful analgesic agent. (C) 2000 Elsevier Science B.V. All rights reserved.