Inhibition of homologous passive cutaneous anaphylaxis (PCA) by disodium cromoglycate-related compounds.

Abstract

Abstract-A study was conducted to examine the effect on homologous PCA in rats of 14 different, newly synthesized compounds, given orally, in relation to the chemical structure of DSCG, when given orally on homologous PCA in rats. The structure activity relationship of these compounds was also discussed. Among the 7 compounds of the glycerol bischromenonyl ether derivatives, 1,3-bis (2-phenyl-4-chromenon-5-yl) oxypropane-2-ol (compound 1) showed the most potent inhibitory activity on PCA. The other compounds showed a moderate or no effect. Two compounds of glycerol bisphenyl ether derivatives had little effect. On the other hand, 1,3-bis (2-carboxy-3 hydroxyphenyl)oxypropane (compound 11) out of alkandiol bisphenyl ether derivatives significantly inhibited PCA, and the other 4 compounds showed a tendency toward inhibition of the reaction. The late inhibition, seen in the biphasic inhibitory pattern induced by compound 11, may be caused by a certain active substance transformed in the body.We have already reported a comparative study on the anti-allergic effects of disodium baicalein 6-phosphate (BPS) as a monochromone derivative, and of disodium cromoglycate (DSCG) as a dichromone derivative. BPS inhibited not only reaginic (IgE) antibody mediated reactions, including antigen-induced mediator release from monkey lung, homologous passive cutaneous anaphylaxis (PCA) in rats, and IgE antibody-mediated degranulation of mast cells, but also non-reaginic antibody-mediated reactions such as mediator release from both guinea pig lung sensitized with egg albumin and human lung caused by anti-IgE. Conversely, DSCG showed characteristic properties as an inhibitor of IgE antibody-mediated reaction. From these findings, it was suggested that the functional site of IgE antibody appears to interact with DSCG, with a definite distance between the two chromone-nuclei ; while the site of the non-reaginic antibody, IgG, is shorter or longer than that of IgE antibody and is readily fixed with two molecules of BPS (1).Meanwhile, the development of DSCG contributed greatly to the therapy for asthma, particulary atopic type asthma (2). The drug, however, is ineffective when given orally, as it is poorly absorbed from the gastrointestinal tract. Such being the case, drugs with a mechanism similar to that of DSCG and are which effective when given orally are most feasible for treatment of patients with asthma, particularly children. Several reports on such drugs have been made (1, 3-9).The present paper describes the effect of oral ingestion of newly synthesized compounds in relation to the chemical structure of DSCG on homologous PCA in rats using their IgE

Pharmacological Characterization of Mouse Ear PCA

“…While PCA can be elicited in many animal species, rat homologous PCA has been widely used for this purpose [2][3][4][5][6], In mice, PCA is usually elicited in dorsal skin and evaluated by means of the diameter or dimension of the lesion [7], In our preliminary experiment, however, PCA in mouse dorsal skin was little reproducible and the di ameter or dimension of PCA site was not always a good parameter for quantitative evaluation. On the other hand, Feinberg [8] reported the availability of mouse ear for PCA.…”

Passive Air-Pouch Anaphylaxis in Rats

“…These agents are reported to inhibit the antigen-induced mediator release and to suppress homologous PCA in rats significantly [3][4][5][6][7], In the present study, these agents suppressed not only increased vascular permeability but also histamine re lease in PAPA ( fig. 1-3).…”

“…In PAPA the increased plasma exudation was closely correlated with the heightened level of histamine in the pouch fluid immediately after the injection of the antigen so lution into the preformed air-pouch sensitized pas sively. As compared with passive cutaneous anaphy laxis (PCA) established by Ovary [2] and widely used for studying antiallergic agents [3][4][5][6][7], PAPA has the advantage that anaphylaxis can be studied quantita tively by measuring plasma exudation and the con tent of chemical mediators such as histamine released from mast cells in the anaphylactic reaction.…”

Passive Air-Pouch Anaphylaxis in Rats

“…While PCA can be elicited in many animal species, rat homologous PCA has been widely used [2][3][4][5][6]. In addition to antiana phylactic agents, several types of agents can inhibit PCA [7][8][9].…”