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
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).


METHODS
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.


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.
Queralt
M
M
Departament de Farmacologia i Terapèutica, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Brazís
P
P
Merlos
M
M
de Mora
F
F
Puigdemont
A
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004285:Dogs; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D017336:Loratadine / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology*; D012867:Skin / Q000166:cytology; D013844:Thiazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000906:Antibodies; D006633:Histamine Antagonists; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; C103639:rupatadine; D003533:Cyproheptadine; D007073:Immunoglobulin E; D000001:Calcimycin; D017336:Loratadine; C071317:Foropafant