Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents

doi:10.1016/0014-2999(93)90201-R

European Journal of Pharmacology

Volume 241, Issues 2–3, 14 September 1993, Pages 183-188

https://doi.org/10.1016/0014-2999(93)90201-R Get rights and content

Abstract

We investigated the xanthine oxidase/xanthine dehydrogenase inhibitory activity and hypouricemic effect of a newly synthesized xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazole-carboxylic acid, and compared its effects with those of allopurinol in rodents. TEI-6720 was found to inhibit bovine milk xanthine oxidase, and mouse liver and rat liver xanthine oxidase/xanthine dehydrogenase with IC₅₀ values of 1.4, 1.8 and 2.2 nM, respectively. On bovine milk xanthine oxidase, TEI-6720 exhibited mixed-type inhibition and the K_i value was 0.7 nM. TEI-6720 displayed prolonged urate-lowering activity in normal mice and rats. We evaluated the hypouricemic effect of TEI-6720 on hyperuricemia induced by the uricase inhibitor, potassium oxonate (250 mg/kg s.c., 1 h before the test drugs), and measured the total molarity of both serum allantoin and urate in rats. Oral TEI-6720 and allopurinol had a hypouricemic effect 2 h after their administration to oxonate-pretreated rats with ED₅₀ values of 1.5 and 5.0 mg/kg, respectively. Both compounds also reduced the combined molarity of uric acid and allantoin in rats. The ED₅₀ values of TEI-6720 and allopurinol were 2.1 and 6.9 mg/kg p.o., respectively. These results suggest that TEI-6720 may be useful for the treatment of hyperuricemia.

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Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents

Abstract

Pharmacol. Res. Commun.

Am. J. Med.

Am. J. Med.

Am. J. Med.

Life Sci.

Am. J. Med.

Biochem. Pharmacol.

Biochem. Pharmacol.

Biochem. Pharmacol.