Hydroxyzine

Hydroxyzine is a histamine H1-receptor antagonist.

Evaluation of anxiolytic effects of aripiprazole and hydroxyzine as a combination in mice.[Pubmed:27999468]

J Basic Clin Pharm. 2016 Sep;7(4):97-104.

CONTEXT: Anxiety disorders are chronic, common, and often comorbid. There is an unmet need in its treatment. Aripiprazole and Hydroxyzine are well-known therapeutic options used as monotherapy in clinics. They have different mechanisms and site of actions. AIM: The objective of the present study was to evaluate the anxiolytic effect of aripiprazole and Hydroxyzine in combination. MATERIALS AND METHODS: Swiss albino mice (male) received treatment of 5% of Tween 80 in 0.9% saline (10 ml/kg; control group), "aripiprazole alone" (1 mg/kg), "Hydroxyzine alone" (3 mg/kg), and aripiprazole (0.5 mg/kg) + Hydroxyzine (1.5 mg/kg) through the intraperitoneal route. RESULTS: The in vivo outcomes (elevated plus maze, light/dark transition, and marble burying tests) of Hydroxyzine monotherapy-treated group showed a significant anxiolytic activity. The combination-treated group was found to be better than control and aripiprazole-treated groups. The combination-treated group showed a significant increase in the level of serotonin in different brain regions as compared to aripiprazole-treated group but not better than the Hydroxyzine group. The in vitro results were in compliance with the in vivo results. The combinational approach was found to be beneficial in anxiolytic treatment as compared to aripiprazole monotherapy. However, Hydroxyzine showed better anxiolytic activity when compared to control, aripiprazole monotherapy, and combination groups. CONCLUSIONS: The anxiolytic effect of combination-treated group was found to be better than aripiprazole monotherapy and lesser than Hydroxyzine monotherapy.

Enantioselective UFLC Determination of Hydroxyzine Enantiomers and Application to a Pharmacokinetic Study in Rabbits.[Pubmed:27621133]

J Chromatogr Sci. 2016 Nov;54(10):1806-1812.

Hydroxyzine is the first generation H1 receptor antagonist drug that is now marketed as a racemic mixture. The paper describes a validated enantioselective liquid chromatography method for the resolution of Hydroxyzine enantiomers and cyclizine (internal standard) from 200 microL of rabbit plasma by liquid-liquid extraction technique using n-hexane and isopropanol. Hydroxyzine enantiomers were resolved at 10.2 and 11.1 min with good baseline resolution (Rs = 1.9) on a Lux amylose-2 chiral column (250 mm x 4.0 mm, 5 microns) at ambient room temperature. The mobile phase consisted of n-hexane-ethanol-diethylamine (90:10:0.1 v/v/v) pumped at 0.9 mL/min. The eluted enantiomers were detected at 254 nm. The linear calibration curve was constructed in the range 20-1000 ng/mL for both the (S)- and (R)-enantiomers. The intra- and inter-day precision were 0.16-2.6% and 0.2-1.92% for (S)-Hydroxyzine and (R)-Hydroxyzine, respectively. The method was successfully applied to determine the kinetic parameters of (S)- and (R)-Hydroxyzine enantiomers in rabbits. The results illustrate that the disposition of Hydroxyzine enantiomers is not stereoselective in rabbits.

Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study.[Pubmed:27712113]

Am J Drug Alcohol Abuse. 2017 Jan;43(1):78-86.

BACKGROUND: Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. OBJECTIVES: This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (Hydroxyzine) would enhance any treatment effect. METHODS: At timepoint T = 0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and Hydroxyzine PO (100 mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. RESULTS: Comparison of average baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 +/- 2.4; palonosetron, 1.5 +/- 0.97; and palonosetron with Hydroxyzine, 0.2 +/- 0.1333. CONCLUSIONS: Pretreatment with palonosetron significantly reduced many signs of experimentally-induced opioid withdrawal. Co-administration with Hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal.