Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-kappaB activity consistent with inverse agonism at the histamine H1 Receptor.
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Wu RL, Anthes JC, Kreutner W, Harris AG, West RE Jr
Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-kappaB activity consistent with inverse agonism at the histamine H1 Receptor.
Int Arch Allergy Immunol. 2004 Dec;135(4):313-8. Epub 2004 Nov 24.
- PubMed ID
- 15564772 [ View in PubMed]
- Abstract
BACKGROUND: The human histamine H1 receptor is constitutively active and exhibits basal activation of nuclear factor-kappaB (NF-kappaB), an important modulator of allergic inflammation. Certain H1 antihistamines have recently been shown to inhibit basal NF-kappaB activity by stabilizing the H1 receptor in an inactive state, a phenomenon called 'inverse agonism'. METHODS: We evaluated the effect of the new H1 antihistamine, desloratadine, on basal and histamine-stimulated NF-kappaB activity and compared it with the activities of other H1 antihistamines. RESULTS: Transiently transfected COS-7 cells co-expressing NF-kappaB-luciferase and the H1 receptor exhibited constitutive NF-kappaB activity. H1 antihistamines reduced basal NF-kappaB activity (rank order of potency: desloratadine > pyrilamine > cetirizine > loratadine > fexofenadine). Histamine stimulated basal NF-kappaB activity 8-fold, which was blocked by H1 antihistamines (rank order of potency: desloratadine > cetirizine > pyrilamine > loratadine > fexofenadine). Neither histamine nor antihistamines had any effect on NF-kappaB activity in the absence of the H1 receptor. CONCLUSIONS: Desloratadine, acting through the histamine H1 receptor, inhibited basal NF-kappaB activity and can thus be classified as an inverse agonist. Inhibition of basal and histamine-stimulated NF-kappaB activity may help to explain previously reported inhibitory effects of desloratadine on allergic inflammatory mediators.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Desloratadine Histamine H1 receptor Protein Humans YesAntagonistDetails