Effects of Rupatadine on Platelet- Activating Factor-Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study)

J Investig Allergol Clin Immunol. 2017;27(3):161-168. doi: 10.18176/jiaci.0117. Epub 2016 Oct 19.


Background and objective: Platelet-activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, for example, in the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with a demonstrated anti-PAF effect, although its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. Objectives: To compare the ability of rupatadine to inhibit PAF-induced MC degranulation with that of desloratadine and levocetirizine and to confirm the dual anti-H1 and anti-PAF activity of rupatadine.

Methods: The human MC line LAD2 and primary MCs (human lung tissue MCs [hLMCs]) were used. MC mediator release was evaluated using the b-hexosaminidase and histamine release assay. The effects of rupatadine (H1 antagonist + PAF receptor antagonist), desloratadine, and levocetirizine (H1 antagonists) on LAD2 and hLMCs were compared. The PAF receptor antagonists WEB2086, BN52021, and CV6209 were also tested. PAF receptor protein expression was evaluated in both LAD2 and hLMCs.

Results: CV6209 and rupatadine inhibited PAF-induced MC degranulation in both LAD2 and hLMCs. In LAD2, rupatadine (5 and 10 µM) and levocetirizine (5 µM), but not desloratadine, inhibited PAF-induced b-hexosaminidase release. Rupatadine (1-10 µM), levocetirizine (1-10 µM), and desloratadine (10 µM) inhibited PAF-induced histamine release. Rupatadine at 10 µM had an inhibitory effect on hLMC degranulation, but levocetirizine and desloratadine did not.

Conclusions: This study shows that rupatadine and, to a lesser extent, levocetirizine, but not desloratadine, inhibit PAF-induced degranulation in both LAD2 and hLMCs. These findings support the dual antihistamine and anti-PAF effect of rupatadine in allergic disorders.

Keywords: CV6209; Desloratadine; LAD2; Levocetirizine; Mast cell; Platelet-activating factor; Rupatadine..

Publication types

  • Comparative Study

MeSH terms

  • Azepines / pharmacology
  • Cell Degranulation / drug effects*
  • Cell Line
  • Cetirizine / pharmacology*
  • Cyproheptadine / analogs & derivatives*
  • Cyproheptadine / pharmacology
  • Fibrinolytic Agents / pharmacology
  • Ginkgolides / pharmacology
  • Histamine H1 Antagonists / pharmacology
  • Histamine H1 Antagonists, Non-Sedating / pharmacology*
  • Humans
  • Lactones / pharmacology
  • Loratadine / analogs & derivatives*
  • Loratadine / pharmacology
  • Mast Cells / drug effects*
  • Platelet Activating Factor / pharmacology
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Membrane Glycoproteins / antagonists & inhibitors
  • Pyridinium Compounds / pharmacology
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Triazoles / pharmacology
  • beta-N-Acetylhexosaminidases / drug effects
  • beta-N-Acetylhexosaminidases / metabolism


  • Azepines
  • Fibrinolytic Agents
  • Ginkgolides
  • Histamine H1 Antagonists
  • Histamine H1 Antagonists, Non-Sedating
  • Lactones
  • Platelet Activating Factor
  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoproteins
  • Pyridinium Compounds
  • Receptors, G-Protein-Coupled
  • Triazoles
  • platelet activating factor receptor
  • CV 6209
  • WEB 2086
  • rupatadine
  • Cyproheptadine
  • levocetirizine
  • Loratadine
  • ginkgolide B
  • beta-N-Acetylhexosaminidases
  • desloratadine
  • Cetirizine