Comparative Studies on the Inhibitory Effects of Calcium Antagonists on Cytosolic Ca2+ Levels Increased by High-Potassium or Glutamate in Cultured Rat Cerebellar Granule Cells

Abstract

ABSTRACT-Theanti-allergic and anti-inflammatory activities of DS-4574, which possesses leukotriene antagonism and inhibits the release of immunologically stimulated mediators such as histamine and leukotrienes, were evaluated in several animal models. DS-4574 had dose-dependent inhibitory effects on IgE-mediated passive cutaneous anaphylaxis and the passive Arthus reaction in rats and the phase I response of Forssman antibody-induced bronchoconstriction.In contrast, this compound had no effect on the phase II response of Forssman antibody-induced bronchoconstriction in guinea pigs, the reverse cutaneous anaphylaxis in rats, complement-dependent hemolysis of sheep erythrocytes and the delayed-type hypersensitivity induced by methylated bovine serum albumin in mice. The results obtained in a double sen sitization with two IgE antibodies suggested that DS-4574, as well as disodium cromoglycate, did not impair antigen-antibody combination but prevents the release of chemical mediators such as histamine. DS-4574 also had a weak inhibitory activity on carrageenin paw edema in rats, arachidonic acid ear edema in mice and adjuvant arthritis in rats. In addition, this compound inhibited increased vascular permeability in rat skin induced by leukotriene D4 and platelet activating factor-induced pleurisy in rats in a dose-dependent manner. These results indicate that DS-4574 inhibited type III allergic reactions in addition to type I allergic reactions and some inflammatory reactions. Therefore, DS-4574 could be useful in the treatment of allergic diseases such as asthma.

Antisecretory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene antagonism, on gastric acid secretion in the pig

“…DS-4574 {6-(2-cyclohexylethyl)- [ 1,3,4] thiadiazolo [3,2-a ]-1,2,3-triazoloE4,5-d]pyrimidin-9(3H)-one} is a synthesized compound which was found to possess both mast cellstabilizing and peptidoleukotriene-antagonistic activities [1][2][3][4][5]. Previously we found that DS-4574 prevented experimental gastric lesions in rats [6,7] and inhibited basal gastric acid secretion in pylorus-ligated rats [6].…”