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  • Title: Molecular pharmacology of antihistamines in inhibition of oxidative burst of professional phagocytes.
    Author: Nosáľ R, Jančinová V, Drábiková K, Perečko T.
    Journal: Gen Physiol Biophys; 2015 Apr; 34(2):209-16. PubMed ID: 25730898.
    Abstract:
    Antihistamines of the H₁and H₃/H₄groups interfere with oxidative burst of human professional phagocytes in vitro. In the concentration of 10 μM, H₁antihistamines of the 1st and 2nd generation inhibited oxidative burst of human neutrophils in the rank order of potency: dithiaden > loratadine > brompheniramine > chlorpheniramine > pheniramine. Of the H₁antihistamines, the most effective was dithiaden in suppressing oxidative burst of whole human blood and dose-dependently the chemiluminescence of isolated neutrophils at extra- and intracellular level. Inhibition of free oxygen radical generation in isolated neutrophils by dithiaden resulted from the inhibition of protein kinase C activation. The potentiation of recombinant caspase-3 by dithiaden is supportive of the antiinflammatory effect of dithiaden and suggestive of increasing the apoptosis of professional phagocytes. Of the H₃/H₄antihistamines, the most effective was JNJ7777120 in decreasing chemiluminescence in whole blood and also at extra- and intracellular sites of isolated neutrophils. JNJ 10191584 and thioperamide were less effective and the latter significantly potentiated free oxygen radical generation intracellularly. The results demonstrated that, compared with the H₃/H₄antihistamines investigated, H₁antihistamines were much more potent in inhibiting free oxygen radical generation in human professional phagocytes. This finding should be taken into account therapeutically.
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