[Anti-allergic effects of tazanolast [butyl 3'-(1H-tetrazol-5-yl) oxanilate, WP-833] metabolites].
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.
Hashimoto
T
T
Research Institute Wakamoto Pharmaceutical Co., Ltd., Kanagawa, Japan.
Edanami
K
K
Naito
A
A
Sano
K
K
Fushimi
H
H
Goto
M
M
D000284:Administration, Oral; D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D001393:Azoles; D006633:Histamine Antagonists; D013189:SRS-A; D013777:Tetrazoles; C036097:butyl 3-(1H-tetrazol-5-yl)oxanilate