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

Abstract.

Objective and design: To examine the inhibitory potential of rupatadine, a new H₁-antihistamine and anti-PAF agent, on histamine and TNF-α release. Comparison with an H₁-antihistamine (loratadine) and a PAF-antagonist (SR-27417A).¶Material: Dispersed canine skin mast cells were used to assess the effect of the drugs tested on FcεRI-dependent and -independent histamine release; the human HMC-1 cell line was used to study TNF-α release.¶Treatment and methods: Before stimulation mast cell populations were treated with increasing concentrations of rupatadine, loratadine and SR-27417A. Histamine and TNF-α release were measured following 15-30 min and 3 h activation, respectively.¶Results: The IC₅₀ for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7 ± 0.4 μM, 3.2 ± 0.7μM and 1.5 ± 0.4 μM, respectively whereas for loratadine the IC₅₀ was 2.1 ± 0.9 μM, 4.0 ± 1.3 M and 1.7 ± 0.5 μM. SR-27417A exhibited no inhibitory effect. Rupatadine, loratadine and SR-27417A inhibited TNF-α release with IC₅₀ 2.0 ± 0.9 μM, 2.1 ± 1.1 M and 4.3 ± 0.6 μM, respectively.¶Conclusions: Rupatadine and loratadine showed similar inhibitory effect on histamine and TNF-α release, whereas SR-27417A only exhibited inhibitory effect against TNF-α.