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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Comparative anti-inflammatory, analgesic, and antipyretic activities of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one and 5-chlorosalicylic acid in rats.

Evidence is presented which indicates that 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b) (1,3)-benzoxazin-9-one (I) and 5-chlorosalicylic acid, its major metabolic end-product, are equally effective as anti-inflammatory and antipyretic agents, while the former is a somewhat more effective analgesic than its metabolite in the rat. However, at the equimolar doses used in this study, I is not ulcerogenic, while 5-chlorosalicylic acid does possess this untoward effect in the fasted rat. Moreover, the LD50 for 5-chlorosalicylic acid (261.0 mg/kg) is approximately 6.5 times less than that of I (1710.0 mg/kg) in the nonfasted rat. These results support the postulation that 5-chlorosalicylic acid is most likely responsible for the pharmacological activity displayed by I; i.e., the latter acts as a carrier or delivery system, allowing attenuation of the toxic properties of its active metabolite.[1]


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