Desloratadine Histamine Receptor antagonist

Desloratadine is the active metabolite of loratadine.

Desloratadine is a competitive antagonist of carbachol-induced contractions in isolated rabbit iris smooth muscle with pA2 of 6.67. [1] This compound binds to the human H1 receptor with Ki value of 0.87 nM in displacing tritiated mepyramine. This compound (100 nM to 10 μM) inhibits both IgE-mediated and non–IgE-mediated generation of the cytokines IL-4 and IL-13 by human basophils. It (300 nM to 100 μM) inhibits both IgE and non–IgE-mediated histamine release from human peripheral blood basophils. This chemical (0.1 μM to 10 μM) is also shown to inhibit platelet-activating factor-induced eosinophil chemotaxis and TNF-α-induced eosinophil adhesion in eosinophils obtained from patients with allergic rhinitis or allergic asthma. [2] It (1 μM-10 μM) dose-dependently inhibits the release of histamine and LTC4 from human basophils. This agent (0.1 μM-10 μM) dose-dependently inhibits IL-13 secretion from basophils activated with IL-3 and PMA from human basophils. This compound (10 μM) pretreatment results in a substantial decrease of the induced cytokine message in cultured basophils. It (10 μM) pretreatment causes approximately an 80% reduction in the IL-4 message accumulated with anti-IgE activation in cultured basophils. This chemical (10 μM) also inhibits the histamine and IL-4 protein secreted into the supernatants of cultured basophils. [3] [³H]Desloratadine binds to the human histamine H1 receptor expressed in CHO cells with Kd of 1.1 nM. It is 52, 57, 194, and 153 times more potent than cetirizine, ebastine, fexofenadine, and loratadine, respectively, in competition-binding studies. [4]

Desloratadine (1 mg/mL, 3 mg/mL and 10 mg/mL) induces a dose-dependent and long lasting mydriasis in the guinea-pig in vivo. [1] This compound inhibits histamine-induced paw edema with ED50 of 0.15 mg/kg in mice. It also inhibits an increase in microvascular permeability in response to a histamine challenge to the upper airway of guinea pigs with ED50 of 0.9 μg. [2] This chemical (5 mg/kg) causes inhibition of oxotremorine-induced tremor by disrupting blood-brain barrier in conscious mice. It (1.0 mg/kg) significantly inhibits oxotremorine-induced (0.00125 mg/kg, 0.0025 mg/kg, and 0.02 mg/kg) decreases in dP/dt indicated by a shift in the dose-response curve to the right in the pithed rat. This compound (1.0 mg/kg) significantly inhibits oxotremorine-induced (0.00125 mg/kg, 0.0025 mg/kg, and 0.02 mg/kg) decreases in dP/dt indicated by a shift in the dose-response curve to the right in the pithed rat. [5]