The effect of a new antihistamine drug, Loderix (EGIS-2062), on stimulus-evoked histamine release from rat peritoneal mast cells

The ability of a new, non-sedative antihistamine drug, Loderix (EGIS-2062), to inhibit stimulus-evoked histamine release from rat peritoneal mast cells has been investigated and compared with that of ketotifen (Zaditen). At low concentrations Loderix preincubated with the cells for 10 min prior to the addition of various stimulants (immune aggregates, ionophore A23187 and compound 48/80) produced a concentration-dependent inhibition of histamine release, while at high concentrations it induced the release of histamine. The IC50 values were calculated as 0.2, 15 and 50 microM by using immune aggregate, (rat IgG2 alpha + anti rat IgG) calcium ionophore and 48/80 as stimulants, respectively. At the IC50 level Loderix was more effective than Zaditen (100 times more effective when immune aggregate and 4 times when 48/80 were used for stimulation). Both drugs had a dual effect on mast cells. The morphological observations confirmed the pharmacological action of the drugs, showing also that the histamine release at high concentrations is due to their cytotoxic effect.