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

Inflamm Res. 2000 Jul;49(7):355-60. doi: 10.1007/PL00000216.


Objective and design: To examine the inhibitory potential of rupatadine, a new H1-antihistamine and anti-PAF agent, on histamine and TNF-alpha 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 FcepsilonRI-dependent and -independent histamine release; the human HMC-1 cell line was used to study TNF-alpha release.

Treatment and methods: Before stimulation mast cell populations were treated with increasing concentrations of rupatadine, loratadine and SR-27417A. Histamine and TNF-alpha 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 microM, 3.2+/-0.7 microM and 1.5+/-0.4 microM, respectively whereas for loratadine the IC50 was 2.1+/-0.9 microM, 4.0+/-1.3 M and 1.7+/-0.5 microM. SR-27417A exhibited no inhibitory effect. Rupatadine, loratadine and SR-27417A inhibited TNF-alpha release with IC50 2.0+/-0.9 microM, 2.1+/-1.1 M and 4.3+/-0.6 microM, respectively.

Conclusions: Rupatadine and loratadine showed similar inhibitory effect on histamine and TNF-alpha release, whereas SR-27417A only exhibited inhibitory effect against TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Calcimycin / pharmacology
  • Cell Line
  • Concanavalin A / pharmacology
  • Cyproheptadine / analogs & derivatives*
  • Cyproheptadine / pharmacology*
  • Dogs
  • Histamine Antagonists / pharmacology*
  • Histamine Release / drug effects*
  • Humans
  • Immunoglobulin E / immunology
  • Loratadine / pharmacology
  • Mast Cells / drug effects*
  • Mast Cells / physiology*
  • Skin / cytology
  • Thiazoles / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antibodies
  • Histamine Antagonists
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • rupatadine
  • Cyproheptadine
  • Immunoglobulin E
  • Calcimycin
  • Loratadine
  • Foropafant