In vitro inhibitory effect of rupatadine on histamine and TNF-alpha release from dispersed canine skin mast cells and the human mast cell line HMC-1

Objective and design: To examine the inhibitory potential of rupatadine, a new H-1-antihistamine and anti-PAF agent, on histamine and TNF-alpha releas e. Comparison with an H-1-antihistamine (loratadine) and a PAF-antagonist ( SR-27417A). Material: Dispersed canine skin mast cells were used to assess the effect o f the drugs tested on Fc epsilon RI-dependent and -independent histamine re lease; the human HMC-1 cell line was used to study TNF-alpha release. Treatment and methods: Before stimulation mast cell populations were treate d with increasing concentrations of rupatadine, loratadine and SR-27417A. H istamine and TNF-alpha release were measured following 15-30 min and 3 h ac tivation, respectively. Results: The IC50 for rupatadine in A23187, concanavalin A and anti-IgE ind uced histamine release was 0.7 +/- 0.4 mu M, 3.2 +/- 0.7 PM and 1.5 +/- 0.4 pM, respectively whereas for loratadine the IC50 was 2.1 +/- 0.9 mu M, 4.0 +/- 1.3 M and 1.7 +/- 0.5 mu M. SR-27417A exhibited no inhibitory effect. Rupatadine, loratadine and SR-27417A inhibited TNF-rr release with IC50 2.0 +/- 0.9 mu M, 2.1 +/- 1.1 M and 4.3 +/- 0.6 mu M, respectively. Conclusions: Rupatadine and loratadine showed similar inhibitory effect on histamine and TNF-alpha release, whereas SR-27417A only exhibited inhibitor y effect against TNF-alpha.