Hydroxyzine dihydrochloride (Hydroxyzine 2HCl) is a histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite CETIRIZINE, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative.

H1 receptor:10 nM-19 nM

In a tail-flick test, intraperitoneal injection of 12.5 mg/kg Hydroxyzine reduced the analgesic effect of morphine in rats; however, an injection of 50 mg/kg Hydroxyzine enhanced the effect of morphine. Furthermore, 500 μM Hydroxyzine significantly decreased the steady-state concentration of etoposide by half, achieving a concentration of 0.055 μM/mL in Sprague-Dawley rats.

At a concentration of 0.1 mM, Hydroxyzine inhibits 50% of Experimental Autoimmune Encephalomyelitis (EAE) exacerbation in Lewis rats and suppresses 70% of mast cell degranulation. In bladder slices pre-treated with Hydroxyzine, a 60-minute incubation results in a 34% inhibition of 5-hydroxytryptamine release induced by 10 μM carbachol, with 1 μM Hydroxyzine causing a 25% inhibition and 0.1 μM suppressing it by 17%. Additionally, 500 μM Hydroxyzine significantly enhances the transport of digoxin to the serosal side in isolated everted jejunum sacs and notably reduces the efflux of approximately 2.4 μg/mL digoxin in the jejunum and ileum.