hydroxyzine brands

Molecular formula: C21H27ClN2O2

The H₁ histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H₁ receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes. Hydroxyzine is a potent inverse agonist of histamine H₁-receptors - inverse agonists are agents that are considered to have a "negative efficacy", so rather than simply blocking activity at a receptor they actively dampen its activity. Inverse agonism at these receptors is responsible for hydroxyzine's efficacy in the treatment of histaminic edema, flare, and pruritus. Hydroxyzine is not a cortical depressant, so its sedative properties likely occur at the subcortical level of the CNS. These sedative properties allow activity as an anxiolytic. Antiemetic efficacy is likely secondary to activity at off-targets. Hydroxyzine does not appear to increase gastric secretions or acidity, and usually has mild antisecretory effects. The antispasmodic activity of hydroxyzine is apparently mediated through interference with the mechanism that responds to spasmogenic agents such as acetylcholine, histamine, and serotonin. Hydroxyzine has CNS depressant, anticholinergic, antispasmodic, and local anesthetic activity, in addition to antihistaminic effects. The drug also has sedative and antiemetic activity. The sedative and tranquilizing effects of hydroxyzine are thought to result principally from suppression of activity at subcortical levels of the CNS; the drug does not have cortical depressant activity. The precise mechanism of antiemetic and antimotion sickness actions of hydroxyzine are unclear, but appear to result, at least in part, from its central anticholinergic and CNS depressant properties. The effects of the drug hydroxyzine on the activities of the rat liver monoamine oxidases (EC 1.4.3.6; MAO) and the membrane-bound and soluble forms of bovine semicarbazide-sensitive amine oxidase (EC 1.4.3.6; SSAO) were studied. Hydroxyzine was found to be a competitive inhibitor of MAO-B (Ki - 38 microM), whereas it had a low potency towards MAO-A (IC50 > 630 microM). Although it was a relatively potent competitive inhibitor of bovine plasma SSAO (Ki approximately 1.5 microM), it was a weak inhibitor of the membrane-bound form of the enzyme from bovine lung (IC50 approximately 1 mM). These findings extend our knowledge of the drug binding capabilities of the amine oxidases and suggest that these interactions may contribute to the complex actions of this drug.

Source: PubChem (NCBI) · compound 3658