ANTIINFLAMMATORY ACTIVITY OF THE ISOQUINOLINE ALKALOID, TETRANDRINE, AGAINST ESTABLISHED ADJUVANT ARTHRITIS IN RATS

Two isoquinoline plant alkaloids, tetrandrine (1) and berbamine (2), h ave been evaluated for anti-inflammatory activity in an acute paw oede ma assay and in adjuvant-induced arthritis in rats. 1 but not 2 suppre ssed the chronic inflammation in the arthritis model but neither compo und was active in the acute inflammation assay. In the adjuvant-induce d polyarthritis, 1 was not effective when given at the time of inocula tion (Day 0), nor just before (Day 7-10) signs of arthritis were evide nt. However, when given on a therapeutic dose schedule (Days 10-13) or continually (Day -1 to +14) on a prophylactic schedule, signs of arth ritis including weight loss due to cachexia were significantly reduced . Given orally, 1 was considerably more potent than aspirin but not ga stro-irritant and may be a promising lead for the development of a saf e and effective treatment of chronic inflammatory diseases.