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pubmed:abstractText |
Guanabenz (2,6-dichlorobenzylidene amino guanidine acetate), an alpha 2-agonist, possesses antiinflammatory activity. Since leukotrienes (LT) and prostaglandins (PG) are proinflammatory substances, the effect of guanabenz on LT and PG synthesis by inflammatory cells was investigated. Guanabenz, but not clonidine, B-HT 920 or B-HT 933 inhibited zymosan-induced LTC4 (IC50 = 13 microM) and PGE2 (IC50 = 10.9 microM) synthesis with no concomitant reduction in zymosan phagocytosis or cell viability. Similarly, guanabenz reduced LTB4 (IC50 = 37.4 microM) and PGE2 (IC50 = 13.8 microM) synthesis by A23187-stimulated rat glycogen elicited neutrophils. Furthermore, guanabenz did not inhibit platelet 12-lipoxygenase or phospholipase A2. In vivo, guanabenz was orally active against rat carrageenan paw edema and adjuvant arthritis (ED50s = 9 and 10 mg/kg, respectively). Topically applied guanabenz reduced arachidonic acid (AA)- or tetradecanoyl phorbol acetate (TPA)-induced ear inflammation (ED50s: AA-induced ear edema, 1.4 mg/ear; PMA-induced ear edema, 0.013 mg/ear). Therefore, the antiinflammatory activity of guanabenz may be due to its ability to inhibit the formation of 5-lipoxygenase and cyclooxygenase products.
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