Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in mice.
The oral administration of mofezolac, [3,4-di(4-methoxyphenyl)-5-isoxazolyl]acetic acid, resulted in the suppression of writhing induced by the intraperitoneal injection of phenyl-p-benzoquinone (phenylquinone, PQ) in mice. The analgesic activity of mofezolac was almost as potent as that of indomethacin, and more potent than that of sodium diclofenac, zaltoprofen, NS-398, and etodolac when their 50% effective doses were compared. The in vitro inhibitory activity of mofezolac against ovine cyclooxygenase (COX)-1 was also more potent than that of any other non-steroidal anti-inflammatory drugs (NSAIDs) tested, whereas the activity of mofezolac against COX-2 was relatively weak. A Western analysis revealed COX-1 to be constitutively expressed, whereas COX-2 was hardly expressed until 30 min after the PQ-injection in the peritoneal cells. Because the writhing terminated within 30 min after PQ-injection, the prostaglandins involved in the induction of writhing seem to be derived from COX-1. These data thus indicate that potent analgesic activity of mofezolac against the present model to be more closely related to its potent inhibitory activity against COX-1 but not against COX-2.
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd., Fukuoka, Japan.
K
K
Goto
H
H
Ochi
Y
Y
Yasunaga
H
H
Matsuyuki
T
T
Imayoshi
H
H
Kusuhara
T
T
Okumoto
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016227:Benzoquinones / Q000633:toxicity*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D007527:Isoenzymes; D007555:Isoxazoles; D008565:Membrane Proteins; C029322:phenylbenzoquinone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C054999:mofezolac