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  • Title: In vitro and in vivo immunopharmacologic properties of a new antiallergic agent RHC 3414.
    Author: Khandwala A, Sonnino-Goldman P, Leibowitz M, Dally-Meade V, Donigi-Ruzza D.
    Journal: Arch Int Pharmacodyn Ther; 1984 Jan; 267(1):103-22. PubMed ID: 6202252.
    Abstract:
    The antiallergic activity profile of RHC 3414 (7-phenylpyrido (3', 2': 4, 5)-thieno (3.2-d)-1, 2, 3-triazine-4(3H)-one) has been compared with that of disodium cromoglycate (DSCG) in several in vitro and in vivo models of anaphylaxis and inflammation. RHC 3414 was approximately 50 times more potent than DSCG as an inhibitor of antigen-induced release of histamine (AIR) from rat mast cells (RMC) in vitro. As an inhibitor of mediator release, the activity profile of RHC 3414 was identical to that of DSCG in the following respects: inhibition of IgE-mediated release of histamine from RMC but not human basophils (HUB), rapid loss of inhibitory activity as a function of time prior to antigen challenge, inability to inhibit the release of histamine from RMC stimulated by non-immunologic secretagogues as well as IgG1-mediated histamine release from guinea-pig lung slices. In vivo, given orally the sodium salt of RHC 3414 (RHC 3414-Z) was a potent inhibitor of passive cutaneous anaphylaxis (PCA) in the rat. Administered intraperitoneally, RHC 3414-Z was approximately 30 times as potent as DSCG as an inhibitor of IgE-mediated PCA in the rat without any antihistaminic or antiserotonin activity. RHC 3414-Z also inhibited adjuvant-induced inflammatory responses in the rat but had no effect on carrageenan-induced edema formation in vivo or on phospholipase A2 or cyclooxygenase activity in vitro. We conclude that RHC 3414 is a potent antiallergic agent with a mechanism of action similar to that of DSCG. In addition, RHC 3414 may possess the ability to inhibit chronic inflammatory processes, an attribute which should prove useful in the prophylactic treatment of asthma.
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