Abstract
A new uricosuric agent, 5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7-carboxylic acid (AA-193) was compared with other uricosurics in the rat, mouse and cebus monkey, because the effects of those drugs were known to be highly species-dependent.
Probenecid and tienilic acid which in the human kidney block the reabsorption of filtered and secreted urate, increased the urate excretion in rats. But benzbromarone, an inhibitor of the latter reabsorption in man, did not have the uricosuric activity. Thus, the post-filtered reabsorption of urate is probably dominant in rats. We found that in rats AA-193 is the most potent uricosuric yet reported. In mice, probenecid not only had so-called paradoxical actions but stimulated the urinary urate wasting after administration of pyrazinamide. Aspirin also responded paradoxically. These data suggested that the renal transport system of urate in the mouse is similar to that in man. AA-193 as well as benzbromarone enhanced the urate excretion dose-dependently in normal condition, but the effects were different in pyrazinamide-suppression tests in mice. In cebus monkeys, the uricosuric and hypouricemic effects of AA-193 were more patent than those of probenecid and similar to those of tienilic acid, but less than those of benzbromarone. Benzbromarone had a considerable role in post-secreted reabsorption in the mokey.
Conclusion: AA-193 is a new class of uricosuric agent that controls the renal reabsorption of filtrated urate particularly.
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Dan, T., Koga, H., Onuma, E. et al. 25 THE ACTIVITY OF AA-193, A NEW URICOSURIC AGENT, IN ANIMALS. Pediatr Res 24, 115 (1988). https://doi.org/10.1203/00006450-198807000-00049
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DOI: https://doi.org/10.1203/00006450-198807000-00049