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 greater than 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 a moderate inhibitor of bull seminal vesicle prostaglandin (PG) synthesis (IC50 = 2.4 X 10(-5) M) and a potent inhibitor of rat brain PG synthesis (IC50 = 4.5 X 10(-6) M) but was ineffective against rat kidney PG synthesis (IC50 7.5 X 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.
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Authors | K R Gans, W Galbraith, R J Roman, S B Haber, J S Kerr, W K Schmidt, C Smith, W E Hewes, N R Ackerman |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 254
Issue 1
Pg. 180-7
(Jul 1990)
ISSN: 0022-3565 [Print] United States |
PMID | 2366180
(Publication Type: Journal Article)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Prostaglandins
- Thiophenes
- Angiotensin II
- DuP 697
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Topics |
- Administration, Oral
- Angiotensin II
(pharmacology)
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology, toxicity)
- Cattle
- Digestive System
(drug effects)
- Prostaglandins
(biosynthesis)
- Rats
- Rats, Inbred Strains
- Renal Circulation
(drug effects)
- Thiophenes
(pharmacology)
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