Anti-allergic effects of tazanolast [butyl 3'-(1H-tetrazol-5-yl) oxanilate, WP-833] metabolites].

T Hashimoto, K Edanami, A Naito, K Sano, H Fushimi, M Goto

Research Institute Wakamoto Pharmaceutical Co., Ltd., Kanagawa, Japan.

Nihon yakurigaku zasshi. Folia pharmacologica Japonica 1990 Apr

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WP-833 is an orally active new antiallergic drug. The effects of WP-833 metabolites on experimental allergic reactions were investigated in various animal models. MTCC [3'-(1H-tetrazol-5-yl) oxanilic acid], the main metabolite of WP-833, dose-dependently inhibited 48-hr homologous passive cutaneous anaphylaxis (PCA) in rats and 8-day PCA in guinea pigs after intravenous administration. The inhibitory effect of MTCC on PCA was nearly equal to that of WP-833. MTCC also inhibited 48hr PCA in rats after the peroral administration, although its inhibitory effect was about 6 times weaker than that of WP-833. MTCC also showed a dose-dependent inhibition on the release of histamine or slow reacting substance of anaphylaxis (SRS-A) from passively sensitized rat peritoneal mast cells and guinea pig lung fragments in vitro with a similar potency to WP-833. MTA [3-(1H-tetrazol-5-yl) aniline] and MTAA [3'-(1H-tetrazol-5-yl) acetanilide], other metabolites of WP-833, inhibited PCA and anaphylactic histamine release from rat peritoneal mast cells at considerably higher doses than WP-833, and they showed no effects on the release of histamine and SRS-A from guinea pig lung fragments. Moreover, only small amounts of MTA and MTAA were detected in the blood after the oral administration of WP-833. From these results, it was suggested that MTCC may be the main active metabolite of WP-833.

Citation

T Hashimoto, K Edanami, A Naito, K Sano, H Fushimi, M Goto. Anti-allergic effects of tazanolast [butyl 3'-(1H-tetrazol-5-yl) oxanilate, WP-833] metabolites]. Nihon yakurigaku zasshi. Folia pharmacologica Japonica. 1990 Apr;95(4):159-66