INHIBITORY EFFECT OF THE H-1 ANTAGONIST LORATADINE ON HISTAMINE-RELEASE FROM HUMAN BASOPHILS

Loratadine is a powerful H-1 antagonist commonly employed in the treat ment of allergic disorders. The present study was performed to investi gate whether loratadine, in addition to anti-Hi activity, is able to m odulate histamine release from human basophils. Leukocyte suspensions were prepared by dextran sedimentation of peripheral venous blood draw n from 10 normal subjects. Leukocytes were stimulated with anti-IgE (1 /5,000), N- formyl-methionyl-leucyl-phenylalanine (FMLP; 10 mu M) and the Ca2+ ionophore A23187 (1 mu M), and histamine release in the cell supernatants was measured by an automated fluorometric method. Loratad ine, at concentrations ranging from 1 to 50 mu M, exerted a dose-depen dent inhibitory effect on IgE-mediated and IgE-independent histamine r elease. The concentrations inhibiting 50% of histamine release were 30 mu M (anti-IgE), 29 mu M (FMLP) and 24 mu M (Ca2+ ionophore A23187). The inhibitory activity of loratadine was optimal after incubation for 2 h at 37 degrees C and the effect of the drug was no longer evident when leukocytes were stimulated 2 h after cell washing. Increased extr acellular Ca2+ concentrations reduced the inhibitory activity of lorat adine, indicating that external Ca2+ and loratadine have antagonistic effects on basophil histamine release. These results indicate that lor atadine, in addition to H-1 receptor blocking activity, has the capaci ty to inhibit histamine release from human basophils.