ANTIINFLAMMATORY AND SAFETY PROFILE OF DUP-697, A NOVEL ORALLY EFFECTIVE PROSTAGLANDIN SYNTHESIS INHIBITOR

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  • 1 July 1990
    • journal article
    • research article
    • Vol. 254  (1) , 180-187
Abstract
DuP 697 (5-bromo-2[4-fluorophenyl]-3-[4-methylsulfonylphenyl]-thiophene) is a potent inhibitor of paw swelling in nonestablished and established adjuvant arthritis in rats (ED50 = 0.03 and 0.18 mg/kg/day, respectively). DuP 697 had no effect on phenylquinone writhing in rats (ED50 > 100 mg/kg), but was analgetic against inflammation-related pain in the Randall-Selitto assay (ED30 = 3.5 mg/kg) and was a very potent antipyretic agent (ED50 0.05 mg/kg). The drug was not ulcerogenic in rats at single doses up to 400 mg/kg. Dup 697 (5 mg/kg i.v.) did not alter renal blood flow or the renal vascular response to angiotensin II in furosemide-pretreated, volume-depleted rats. In contrast, indomethacin (5 mg/kg i.v.) decreased renal blood flow and potentiated the renal vascular response to angiotensin II in these animals. DuP 697 was moderate inhibitor of bull seminal vesicle prostaglandin (PG) synthesis (IC50 = 2.4 .times. 10-5 M) and a potent inhibitor of rat brain PG synthesis (IC50 = 4.5 .times. 10-6 M) but was ineffective against rat kidney PG synthesis (IC50 7.5 .times. 10-5 M). These differential effects of DuP 697 on PG synthesis by various tissues may account for its high potency as an anti-inflammatory and antipyretic agent and its minimal toxicity profile.