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

Nihon Yakurigaku Zasshi. 1990 Apr;95(4):159-66. doi: 10.1254/fpj.95.4_159.
[Article in Japanese]

Abstract

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Azoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Guinea Pigs
  • Histamine Antagonists / administration & dosage
  • Histamine Antagonists / pharmacology*
  • Histamine Release / drug effects*
  • In Vitro Techniques
  • Lung / metabolism
  • Male
  • Mast Cells / metabolism
  • Passive Cutaneous Anaphylaxis / drug effects*
  • Rats
  • Rats, Inbred Strains
  • SRS-A / metabolism
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacology*

Substances

  • Azoles
  • Histamine Antagonists
  • SRS-A
  • Tetrazoles
  • butyl 3-(1H-tetrazol-5-yl)oxanilate