Abstract
This anti-inflammatory agent proved to have a therapeutic margin wider than that of indomethacin. Y-8004 exhibited little effect on the central nervous system, somatic and autonomic nervous system. On the cardiovascular system in dogs, Y-8004 induced a slight transient fall in blood pressure followed by a pressor response, increase in heart rate and coronary vasodilation at a dose of 30 mg/kg given intravenously, but no remarkable change was seen on the electrocardiogram. Y-8004 showed no effect on isolated smooth muscles such as vas deferens, ileum and atria, but inhibited gastrointestinal propulsion at a dose of 100 mg/kg given orally in mice and spontaneous contractions of the pregnant uterus of rats at a concentration of more than 10(-6)M. This agent also decreased urine volume and electrolytes in rats. This property was considered to be common to other acidic nonsteroidal anti-inflammatory agents. On the other hand, in guinea pigs, Y-8004 inhibited the bradykinin-induced bronchoconstriction and the collagen-induced platelet aggregation to a greater extent than did indomethacin. These findings suggest that Y-8004 is an active compound with properties similar to acidic non-steroidal anti-inflammatory agents such as indomethacin.
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