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The role of mast cells can be protective or harmful: depending upon the physiological/pathological condition in which they get activated. The latter role is due to mast cell degranulation and the release of an array of incendiary mediators. Mast cells have a well-established role in diseases like allergy, eczema, anaphylactic shock, mastocytosis, and other miscellaneous mast cell disorders. The derivatives of spiro-beta-carboline were evaluated for mast cell stabilization activity by compound 48/80 induced degranulation histamine release assay. The mast cell stabilization of 2'-Heptyl-2',3',4',9'-tetrahydrospiro[cyclohexane-1,1'-pyrido[3,4-b]indole]-3'-carboxylic acid (IC50 = 0.389 ± 0.015 miM) and 2'-Benzoyl 2',3',4',9'-tetrahydrospiro[cyclohexane-1,1'-pyrido[3,4-b]indole]-3'-carboxylic acid (IC50 = 00.469 ± 0.032 miM) compounds were to be of similar potency as that of standard drug sodium cromoglycate (IC50 =0.489 ± 0.003miM).