General pharmacology of the butanamide derivative S 19812, a new dual inhibitor of cyclooxygenase and lipoxygenase pathways.
S 19812 (N-hydroxy-N-methyl-4-(2,3-bis-(4-methoxyphenyl)-thiophen-5-yl) butanamide, CAS 181308-68-9), a dual inhibitor of cyclooxygenase and lipoxygenase pathways, was evaluated in different models of pain and inflammation. Its gastric tolerance was also investigated. After acute oral treatment S 19812 exhibited a non-opioid analgesic activity observed in the phenylbenzoquinone-induced writhing model in mice (ED50 = 2.1 mg/kg) and in the carrageenan-induced hyperalgesia model in rats (ED50 = 9.1 mg/kg, preventive treatment; 8.3 mg/kg, curative treatment). Anti-inflammatory activity was observed in the adjuvant-induced arthritis in rat (inhibition of edema ED50 = 11 mg/kg/day p.o., day 28). In rats and mice, S 19812 exhibited an excellent gastric tolerance at doses up to 800 mg/kg p.o.
Tordjman
Charles
C
Division of Rheumatology, Institut de Recherches Servier, Suresnes, France.
Andre
Nathalie
N
Bresson
Yvette
Y
Bellot
Isabelle
I
Deschamps
Christine
C
Pastoureau
Phlippe
P
Wierzbicki
Michel
M
D019342:Acetic Acid; D000388:Air; D000577:Amides / Q000494:pharmacology* / Q000633:toxicity; D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology; D013876:Thiophenes / Q000494:pharmacology* / Q000633:toxicity
D000577:Amides; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D009292:Narcotic Antagonists; D013876:Thiophenes; C480199:N-hydroxy-N-methyl 4-(2,3-bis-(4-methoxyphenyl)-thiophen-5-yl)butanamide; D009270:Naloxone; D002351:Carrageenan; D015232:Dinoprostone; D019342:Acetic Acid