EVALUATION OF ANTIPYRETIC AND ANTINOCICEPTIVE POTENTIAL OF NEW HETEROCYCLIC DERIVATIVES OF 3-FORMYL-4-HYDROXYCOUMARIN IN RATS

Abstract

Coumarins have multiple biological activities; various coumarin-related derivatives are recognized as inhibitors of the lipoxygenase and cycloxygenase pathways of arachidonate metabolism. Several natural or synthetic coumarins with various hydroxyl and other substitutes were found to inhibit lipid peroxidation and to scavenge hydroxyl radical and superoxide anion and to influence processes involving free radical mediated injury. Thus, the objective of the present study was to evaluate the antipyretic and analgesic activities of heterocyclic derivatives of 3-formyl-4-hydoxycoumarin (synthesized by us) in animal models. All compounds synthesized were evaluated for the above activity and their effects were compared with the standard drugs. In the antipyretic test, a new model of pyrexia suggested by Tomazetti et al., 2005 was used where backer’s yeast is used to induce pyrexia in juvenile male Wistar rats, which received Backer’s yeast at 135 mg/kg intraperitonealy. The test compound or Paracetamol was given orally 1 h after injection of yeast (when average rise in rectal temp was about 1 ºC). Meanwhile, in the analgesic test the nociceptive response using hot plate and formalin tests were performed in adult male Wistar rats. The test compounds (heterocyclic derivatives of 3-formyl-4-hydoxycoumarin) showed significant antipyretic activity in rats. The test compound also produced significant antinociceptive activity in the hot plate (central) as well as in formalin tests (central and peripheral) nociceptive tests suggesting the involvement of both central and peripheral mechanisms in alleviating the pain response.