ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF 6-CHLORO-5-CYCLOHEXYLINDAN-1-CARBOXYLIC ACID (TAI-284)

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Since the discovery of adramatically potent antiphlogistic or antirheumatic effect of cortisone, a number of glucocorticoid derivatives were synthesized for pharmacological evaluation and some of them have been introduced to clinical use in rheumatic diseases and other various inflammatory disorders. The large doses or prolonged use of glucocorticoids, however, produced a variety of clinical side effects such as gastro-intestinal lesion and impaired protection against infection mainly due to adaptative adrenal atrophy and immunosuppression. Enthusiastic efforts to dissociate the therapeutic effects from adverse ones in chemical structure of glucocorticoids have all resulted in failure.<BR> Consequently, chemical and pharmacological investigations to search for new nonsteroidal antiphlogistics different in mode of action from glucocorticoids and less in toxicity have been revived with successful introduction of some agents on the market. They consist of a variety of chemical compounds including weak organic acids such as phenylbutazone, ibufenac, and indomethacin, and moderately strong base such as benzydamine.<BR> Research largely concentrated upon various weak organic acids effective against inflammatory processes in experimental animals in this laboratory has resulted in presentation of 6-chloro-5-cyclohexylindan-1-carboxylic acid (TAI-284), which has strong antiinflammatory, analgesic, and antipyretic activities. The structure is as follows:<BR> Since no single assessment can represent the general aspects of the drug and provides a satisfactory evaluation for anti-inflammatory agents in the screening process (1), a variety of phlogistic materials, experimental animals, or sites of inflammation are required. In addition, according to Winter (2) certain less specific means of producing inflammation in the screening methods may give an efficient evaluation of anti-inflammatory agents clinically used.<BR> Therefore, to assess the anti-inflammatory activities of TAI-284, a variety of substances such as carrageenin, kaolin, acetic acid, croton oil, sodium urate, and Freunds complete adjuvant were used as phlogistic agents, and ultraviolet irradiation and cotton pellets were also applied.
社団法人日本薬理学会の論文

ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF 6-CHLORO-5-CYCLOHEXYLINDAN-1-CARBOXYLIC ACID (TAI-284)

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