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 2 response (10-60 min) of the formalin test in rats. This effect was 3 times less potent than that of indomethacin. FR122047 (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(1alpha) level in acetic acid-injected mouse peritoneal cavity. However, a selective cyclooxygenase-2 inhibitor, NS-398, had no effect in these cyclooxygenase-1 sensitive pain models. These results suggest that FR122047, a selective cyclooxygenase-1 inhibitor, shows an analgesic effect in chemical nociceptive models and may be a useful analgesic agent.
Ochi
T
T
Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical, 1-6, Kashima 2-chome, Yodogawa-ku, Osaka, Japan.
Motoyama
Y
Y
Goto
T
T
D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005557:Formaldehyde; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009578:Nitrobenzenes / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D000700:Analgesics; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D010879:Piperazines; D011453:Prostaglandins; D013449:Sulfonamides; D013844:Thiazoles; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C085131:1-((4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl)-4-methylpiperazine; D005557:Formaldehyde; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C496513:Ptgs1 protein, rat; D019342:Acetic Acid; D007213:Indomethacin