Antiallergic action of 6-ethyl-3-(1h-tetrazol-5-yl) chromone (aa-344) on immediate hypersensitivity reaction in rats

Abstract

Abstract-A newly synthesized compound, 6-ethyl-3-(IH-tetrazol-5-yl)chromone (AA-344) given intravenously or orally inhibited considerably the 72-hr passive cutaneous anaphylaxis (72-hr PCA) induced by IgE in rats. The antiallergic action of AA-344 was neither due to the antihistamine or antiserotonin effect nor was it mediated via adrenergic mechanisms.The results obtained in a double sensitization with two IgE antibodies suggest that AA-344 may not impair antigen-antibody combi nation but probably prevents the release of chemical mediators including histamine. This assumption was supported by observation that AA-344 inhibited a reduction in the skin histamine content caused by the 72-hr PCA, without effect on the compound 48/80-induced histamine reduction. AA-344 also partially inhibited the IgGa-mediated 3-hr PCA in rats. These results indicate that the inhibitory action of AA-344 on the immediate hypersensitivity reactions is due to prevention of the release of chemical mediators from the mast cells, by acting on some process in sequential events leading to the mediator release following antigen-antibody combination.

INHIBITORY ACTION OF 6-ETHYL-3-(lH-TETRAZOL-5-YL)CHROMONE (AA-344) ON IgE-, IgGa- OR CHEMICAL AGENT-INDUCED HISTAMINE RELEASE FROM ISOLATED RAT MAST CELLS

“…AA-344 significantly inhibited the IgGa-mediated PCA reaction in rats, though was much less effective in comparison with that on the IgE-mediated PCA (1). In the present study, AA-344 significantly inhibited the IgGa-mediated histamine release from isolated peritoneal cells containing mast cells, though the inhibitory effect did not attain the level of more than 50%, like that of DSCG.…”

“…We have suggested that the inhibitory action of AA-344 on the PCA may be due to inhibition of the release of the chemical mediators from the mast cells, because AA-344 has no antago nistic action on either histamine or serotonin (1). The present study was done to evaluate the in vitro inhibitory effect of AA-344 on the release of histamine from isolated rat peritoneal mast cells mediated by IgE and IgGa antibodies or that induced by chemical agents.…”

“…In a previous study, we found that 6-ethyl-3-(1H-tetrazol-5-y1) chromone (AA-344) inhibits markedly the IgE-mediated passive cutaneous anaphylaxis (PCA) and partially the IgGa-mediated PCA in rats (1). Both PCA reactions are caused by chemical mediators such as histamine released from mast cells as a result of the immunological reaction (2,3).…”

“…Antisera: Rat anti-DNP-asc antiserum containing IgE (anti-DNP-asc) and rat anti-EA antiserum containing IgGa (anti-EA) were prepared as described previously (1). The titer of anti-DNP-asc, i.e.…”

Antiallergic properties of an orally effective agent,((3-(1H-tetrazol-5-yl)-phenyl)amino) oxoacetic acid n-butyl ester.

“…DSCG, however, is not absorbed orally to any significant extent, and its effectiveness was brought about by an aerosol preparation. Considerable interest has been stimulated in the development of agents for prophylaxis in allergic asthma which are effective by an oral route (4)(5)(6). This report describes the immunopharmacology of a newly synthesized compound,…”