Inhibitory Effect of the H₁ Antagonist Loratadine on Histamine Release from Human Basophils

Abstract

Loratadine is a powerful H₁ antagonist commonly employed in the treatment of allergic disorders. The present study was performed to investigate whether loratadine, in addition to anti-H₁ activity, is able to modulate histamine release from human basophils. Leukocyte suspensions were prepared by dextran sedimentation of peripheral venous blood drawn from 10 normal subjects. Leukocytes were stimulated with anti-IgE (1/5,000), N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10 μM) and the Ca²⁺ ionophore A23187 (1 μM), and histamine release in the cell supernatants was measured by an automated fluorometric method. Loratadine, at concentrations ranging from 1 to 50 μM, exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent histamine release. The concentrations inhibiting 50% of histamine release were 30 μM (anti-IgE), 29 μM (FMLP) and 24 μM (Ca²⁺ ionophore A23187). The inhibitory activity of loratadine was optimal after incubation for 2 h at 37°C and the effect of the drug was no longer evident when leukocytes were stimulated 2 h after cell washing. Increased extracellular Ca²⁺ concentrations reduced the inhibitory activity of loratadine, indicating that external Ca²⁺ and loratadine have antagonistic effects on basophil histamine release. These results indicate that loratadine, in addition to H₁ receptor blocking activity, has the capacity to inhibit histamine release from human basophils.

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

“…The inhibitory properties of rupatadine on MC degranulation are in agreement with those observed by several H 1 -antihistamines (e. g, terfenadine, cetirizine and azelastine) [1,14,22], although the exact mechanism of action remains unknown [22]. Miadonna et al [18], in a study with loratadine, suggested that it affects a common step implicated in biochemical events that provokes the cellular calcium influx, MC activation and exocytosis. Due to the chemical similarities and the inhibitory profiles of rupatadine and loratadine, we think that both compounds may act at the same level, although further studies on cytosolic Ca 2+ levels will be required to elucidate the mechanism.…”

“…Now, we have examined the effects of rupatadine, in comparison to loratadine and SR-27417A, on histamine release from dog skin MC challenged with FceRI-dependent and -independent stimuli. Anti-IgE antibody induces mem- brane-IgE-cross linking, leading to aggregation of the FceRI receptors causing MC degranulation and histamine release [18]. Con A is a lectin that may directly cross-link FceRI receptors and trigger the degranulation process [19,20].…”

Betamethasone prevents virus‐induced airway inflammation but not airway hyperresponsiveness in guinea pigs

“…The conclusion of the authors was that the inhibition of mediator release by loratadine may provide an additional action which contributes to its therapeutic effectiveness. More recently, similar results were obtained on human basophils (IC 50 of 30 mM on histamine release) [2]. The conclusion of the authors were more mitigated than in the previous paper.…”

H1‐receptor antagonists: effects on leukocytes, myth or reality?

“…The conclusion of the authors was that the inhibition of mediator release by loratadine may provide an additional action which contributes to its therapeutic effectiveness. More recently, similar results were obtained on human basophils (IC 50 of 30 μM on histamine release) [2]. The conclusion of the authors were more mitigated than in the previous paper.…”