Antiallergic activity of 6-(2-cyclohexylethyl)-[1,3,4]thiadiazolo- [3,2-a]-1,2,3-triazolo-[4,5-d]pyrimidin-9(3H)-one (DS-4574) in rats

• Published in: International archives of allergy and immunology Vol. 98; no. 2; p. 146
• Main Authors: Aibara, S, Mori, M, Tsubokawa, M, Iwamoto, T, Tsukada, W
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-1992
• Subjects: Adrenalectomy; Anaphylaxis - physiopathology; Animals; Capillary Permeability - drug effects; Histamine - pharmacology; Histamine Release - drug effects; Hypersensitivity - drug therapy; Leukotriene Antagonists; Lung - immunology; Male; Passive Cutaneous Anaphylaxis; Peritoneal Cavity; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Rats; Rats, Inbred Strains; Serotonin - pharmacology; Time Factors; Triazoles - pharmacology; Triazoles - therapeutic use
• ISSN: 1018-2438
• DOI: 10.1159/000236178

The antiallergic activity of DS-4574 was evaluated in several commonly used rat models for allergic diseases. In passive cutaneous anaphylaxis, DS-4574 given intravenously and orally induced dose-dependent inhibition with ID50 values of 0.55 and 2.8 mg/kg, respectively. In contrast, this compound had no antagonistic activity against the histamine- and serotonin-induced cutaneous vascular permeability. In lung anaphylaxis, DS-4574 inhibited pulmonary function changes induced by the antigen in a dose-dependent manner when it was given intravenously and orally, the ID50 values being 0.04 and 0.89 mg/kg, respectively. DS-4574 also inhibited antigen-induced histamine and leukotriene release in passive peritoneal anaphylaxis following oral administration. In addition, this compound prevented antigen-induced histamine release in passively sensitized mast cells in vitro. These potent activities of DS-4574 in in vivo and in vitro models of immediate-type hypersensitivity reactions suggest that this compound could be useful in the treatment of allergic diseases including asthma.