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 Ki 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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Authors | Y Osada, M Tsuchimoto, H Fukushima, K Takahashi, S Kondo, M Hasegawa, K Komoriya |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 241
Issue 2-3
Pg. 183-8
(Sep 14 1993)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 8243554
(Publication Type: Journal Article)
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Chemical References |
- Gout Suppressants
- Thiazoles
- Febuxostat
- Uric Acid
- Allantoin
- Allopurinol
- Xanthine Dehydrogenase
- Xanthine Oxidase
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Topics |
- Allantoin
(blood)
- Allopurinol
(pharmacology)
- Animals
- Cattle
- Febuxostat
- Gout Suppressants
(pharmacology)
- Male
- Mice
- Mice, Inbred ICR
- Rats
- Rats, Sprague-Dawley
- Thiazoles
(pharmacology)
- Uric Acid
(blood)
- Xanthine Dehydrogenase
(antagonists & inhibitors)
- Xanthine Oxidase
(antagonists & inhibitors)
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