title: 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.
abstract: 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.
authors.affiliation: Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Aibara
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Tsubokawa
authors.forename: T
authors.initials: T
authors.lastname: Iwamoto
authors.forename: W
authors.initials: W
authors.lastname: Tsukada
mesh_terms: D000315:Adrenalectomy; D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy*; D020024:Leukotriene Antagonists; D008168:Lung / Q000276:immunology; D008297:Male; D010323:Passive Cutaneous Anaphylaxis; D010529:Peritoneal Cavity; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D020024:Leukotriene Antagonists; D011743:Pyrimidines; D014230:Triazoles; C076052:DS 4574; D012701:Serotonin; D006632:Histamine