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Agents and Actions

, Volume 12, Issue 5, pp 684–690 | Cite as

The analgesic and anti-inflammatory profile of (±)-5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2a]pyrrole-1-carboxylic acid (RS-37619)

  • W. H. RooksII
  • A. J. Tomolonis
  • P. J. Maloney
  • M. B. Wallach
  • M. E. Schuler
Immunosuppression and Inflammation

Abstract

RS-37619 showed highly potent analgesic activity when given p.o. in tests utilizing underlying inflammation. It inhibited phenylquinone-induced writhing in the mouse and rat (350 and 180×aspirin respectively) and the pain induced by flexing the adjuvant-inflamed rat paw (∼ 800×aspirin). The agent increased the pain threshold of compressed yeast-inflamed rat paws (3–10 ×naproxen). RS-37619 did not increase the pain threshold of the noninflamed paw and was inactive in the mouse hot plate test; therefore it is probably not a centrally acting or morphinelike agent. RS-37619 was also highly active p.o. in rat models of acute and chronic inflammation. It inhibited carrageenan-induced paw edema (36×phenylbutazone), cotton pellet-induced granuloma (≤1×indomethacin) and in an 18-day test, prevented the development of adjuvant-induced arthritis (∼2×naproxen). RS-37619 exhibited antiphlogistic activity in adrenalectomized rats. It did not have corticosteroid activity. When given p.o., RS-37619 lowered yeast-induced pyrexia (20×aspirin). Gastro-intestinal irritation was seen in the rat with doses ≥6.4 mg/kg/day p.o. The agent elicited mild CNS and cardiovascular activity only at doses far in excess of those required for analgesic and anti-inflammatory activity.

Keywords

Naproxen Pain Threshold Phenylbutazone Underlying Inflammation Potent Analgesic Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag 1982

Authors and Affiliations

  • W. H. RooksII
    • 1
  • A. J. Tomolonis
    • 1
  • P. J. Maloney
    • 1
  • M. B. Wallach
    • 1
  • M. E. Schuler
    • 1
  1. 1.Department of Bioassay and PharmacologySyntex (USA) Inc., Research DivisionPalo AltoUSA

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