title: REV 2871 (CHBZ): a potent antiallergic agent with a novel mechanism of action. II. Studies on the mechanism of action.
abstract: REV 2871 (CHBZ) was taken up by rat mast cells and human leukocytes in a specific and saturable manner. The compound can be hydrolyzed by a granule-associated enzyme in the mast cell to an ionic metabolite (REV 3579) whose in vitro profile is identical to that of disodium cromoglycate (DSCG). REV 3579, although achieving millimolar concentrations inside cells incubated with CHBZ, was not itself taken up by rat mast cells or human leukocytes. The unusual in vitro activity of CHBZ is postulated to arise from the fact that it is a prodrug for delivering a DSCG-like drug to the interior of a secretory cell. The internalized drug apparently exerts a more general and longer-lived inhibition of the secretory process than it can by acting on exterior membrane receptors. CHBZ thus represents a novel drug for studying anaphylactic responses in vitro.
mesh_terms: D000215:Acylation; D000818:Animals; D001667:Binding, Competitive; D004205:Cromolyn Sodium / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D010080:Oxazoles / Q000378:metabolism* / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats
chemical_list: D006634:Histamine H1 Antagonists; D010080:Oxazoles; C049843:2-ethoxyethyl 5-chlorobenzoxazole-2-carboxylate; D004205:Cromolyn Sodium