Hydroxyzine-d8 is intended for use as an internal standard for the quantification of hydroxyzine by GC- or LC-MS. Hydroxyzine is a histamine H1 receptor antagonist (Ki = 1.9 nM).1 It binds competitively with the H1 receptor inverse agonist mepyramine with an IC50 value of 80 µM in polymorphonuclear leukocytes.2 In vivo, it is metabolized to the H1 receptor antagonist cetirizine .3 In situ, hydroxyzine (10 µM) prevents recruitment of rolling leukocytes induced by histamine in rat mesentery post-capillary venules.4 Hydroxyzine also decreases anxiety-like behavior in mice, increasing the time spent in the open arms of the elevated plus maze and in the light side of the light-dark exploration test.5 Formulations containing hydroxyzine have been used in the treatment of anxiety and as antihistamines in the treatment of allergic rhinitis.
1.Gillard, M., Van Der Perren, C., Moguilevsky, N., et al.Binding characteristics of cetirizine and levocetirizine to human H1 histamine receptors: Contribution of Lys191 and Thr194Mol. Pharmacol.61(2)391-399(2002) 2.Wescott, S., and Kaliner, M.Histamine H1 binding site on human polymorphonuclear leukocytesInflammation7(3)291-300(1983) 3.Obach, R.S.Pharmacologically active drug metabolites: Impact on drug discovery and pharmacotherapyPharmacol. Rev.65(2)578-640(2013) 4.Asako, H., Kurose, I., Wolf, R., et al.Role of H1 receptors and P-selectin in histamine-induced leukocyte rolling and adhesion in postcapillary venulesJ. Clin. Invest.93(4)1508-1515(1994) 5.Sawantdesai, N.S., Kale, P.P., and Savai, J.Evaluation of anxiolytic effects of aripiprazole and hydroxyzine as a combination in miceJ. Basic Clin. Pharm.7(4)97-104(2016)