The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
Immunopharmacological Studies on TBX, a New Antiallergic Drug (1) Inhibitory Effects on Passive Cutaneous Anaphylaxis in Rats and Guinea Pigs
Yukiyoshi YANAGIHARAHiroshi KASAIToshio KAWASHIMATakao SHIDA
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1988 Volume 48 Issue 1 Pages 91-101

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Abstract

The effects of 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1, 2-a]pyrimidin-4-one potassium salt (TBX), a new antiallergic drug, on passive cutaneous anaphylaxis (PCA) mediated by homologous IgE or IgG antibody were investigated in rats and guinea pigs. TBX (i.v. and p.o.) clearly inhibited IgE- and IgGa-mediated homologous PCAs in rats, without showing any inhibition of the skin reactions caused by histamine, serotonin and bradykinin in contrast to the inhibition of prostaglandin E1-induced skin reaction. Neither adrenalectomy nor propranolol treatment modified TBX's inhibition of the former PCA. With regard to tachyphylaxis to TBX, it was demonstrable in IgE-mediated homologous PCA in rats when they were pretreated with TBX (0.5 mg/kg, i.v.), followed 60 min later by a second dose of the drug (0.05 mg/kg, i.v.). There was no cross-tachyphylaxis between disodium cromoglycate (DSCG) and TBX. Homologous PCA caused by guinea pig IgE was also inhibited in a dose-dependent fashion by i.v. and p.o. administrations of TBX, although higher doses of TBX were needed to inhibit guinea pig PCA than the rat one. Interestingly, TBX showed more potent inhibition of both rat and guinea pig homologous PCAs than DSCG or tranilast. The results obtained indicate that TBX is an orally effective antiallergic agent displaying no antagonistic actions on the chemical mediators released.

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