Uricosuric effect of zotepine and its action mechanism

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Zotepine(2-chloro-11-(2-diethyl-aminoethoxy)dibenzo[b.f.]thiepin)has been reported to decrease serum uric acid levels in schizophrenics. We have investigated its uricosuric effect by uric acid clearance, inosine loading test, and PZA suppression test.<BR>Oral administration of 20 mg of zotepine to 3 normal volunteers resulted in moderate uricosuria in 2 or 3 hours, which paralleled the increase of the serum concentration of the drug. In 20 gouty subjects, after administration of zotepine 20mg/day for 14 days, uric acid clearance revealed a decrease of uric acid (1.5±1.8mg/dl). Inosine loading test showed increases of SUA, UUA and CUA. These changes were similar to those of benzbromarone (potent uricosuric agent), but different from those of allopurinol (uric acid production inhibitor), and suggested that zotepine is an uricosuric agent.<BR>In a normal volunteer, who was given 4g of PZA previously, zotepine- induced uricosuria disappeared. PZA is a potent tubular secretion inhibitor. Therefore, zotepine may inhibit tubular secretion, or postsecretory tubular reabsorption.