HYDROXYZINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H27ClN2O2
Molecular Weight	374.905
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc(cc1)C(c2ccc(cc2)Cl)N3CCN(CC3)CCOCCO

InChI

InChIKey=ZQDWXGKKHFNSQK-UHFFFAOYSA-N

InChI=1S/C21H27ClN2O2/c22-20-8-6-19(7-9-20)21(18-4-2-1-3-5-18)24-12-10-23(11-13-24)14-16-26-17-15-25/h1-9,21,25H,10-17H2

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00557
Curator's Comment:: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048,011795s025lbl.pdf

Hydroxyzine, a piperazine antihistamine structurally related to buclizine, cyclizine, and meclizine, is used to treat histamine-mediated pruritus or pruritus due to allergy, nausea and vomiting, and, in combination with an opiate agonist, anxiolytic pain. Hydroxyzine is also used as a perioperative sedative and anxiolytic and to manage acute alcohol withdrawal. Hydroxyzine competes with histamine for binding at H1-receptor sites on the effector cell surface, resulting in suppression of histaminic edema, flare, and pruritus. The sedative properties of hydroxyzine occur at the subcortical level of the CNS. Secondary to its central anticholinergic actions, hydroxyzine may be effective as an antiemetic. It is used for symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Target ID: Leishmania (L.) infantum promastigotes viability Sources: https://www.ncbi.nlm.nih.gov/pubmed/24905294	Inhibitor 7728	59.57 µM [IC50]
Histamine H1 receptor 304 Target ID: CHEMBL231 Sources: http://www.drugbank.ca/drugs/DB00557	Antagonist 2575
Monoamine oxidase B 66 Target ID: CHEMBL2993 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17447421	Inhibitor 7728	38.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 245 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048,011795s025lbl.pdf	Palliative		Approved 8043	VISTARIL Approved Use For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested. Useful in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses, and in histamine-mediated pruritus. Launch Date 7.8589441E11
Pruritus 27 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048,011795s025lbl.pdf	Palliative		Approved 8043	VISTARIL Approved Use For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested. Useful in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses, and in histamine-mediated pruritus. Launch Date 7.8589441E11

C_max

Value	Dose	Analyte	Population
31.371 ng/mL EXPERIMENT http://mri.cts-mrp.eu/download/DK_H_2313_001_PAR.pdf	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
72.5 ng/mL EXPERIMENT https://www.jacionline.org/article/0091-6749(84)90486-X/pdf	0.7 mg/kg bw single, oral dose: 0.7 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
72.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6141198/	0.7 mg/kg bw single, oral dose: 0.7 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYZINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
479.174 ng × h/mL EXPERIMENT http://mri.cts-mrp.eu/download/DK_H_2313_001_PAR.pdf	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROXYZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
18.4 h EXPERIMENT http://mri.cts-mrp.eu/download/DK_H_2313_001_PAR.pdf	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
20 h EXPERIMENT https://www.jacionline.org/article/0091-6749(84)90486-X/pdf	0.7 mg/kg bw single, oral dose: 0.7 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
20 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6141198/	0.7 mg/kg bw single, oral dose: 0.7 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	HYDROXYZINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg 3 times / day multiple, oral Highest studied dose Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/365920	unhealthy, 19 - 34 yars n = 19 Health Status: unhealthy Condition: seasonal allergic rhinitis Age Group: 19 - 34 yars Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/365920	Disc. AE: Drowsiness... Other AEs: Drowsiness, Dry mouth... AEs leading to discontinuation/dose reduction: Drowsiness (1 patient) Other AEs: Drowsiness (17 patients) Dry mouth (12 patients) Irritability (7 patients) Dizziness (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/365920

AEs

AE	Significance	Dose	Population
Drowsiness	1 patient Disc. AE	50 mg 3 times / day multiple, oral Highest studied dose Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/365920	unhealthy, 19 - 34 yars n = 19 Health Status: unhealthy Condition: seasonal allergic rhinitis Age Group: 19 - 34 yars Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/365920
Dry mouth	12 patients	50 mg 3 times / day multiple, oral Highest studied dose Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/365920	unhealthy, 19 - 34 yars n = 19 Health Status: unhealthy Condition: seasonal allergic rhinitis Age Group: 19 - 34 yars Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/365920
Drowsiness	17 patients	50 mg 3 times / day multiple, oral Highest studied dose Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/365920	unhealthy, 19 - 34 yars n = 19 Health Status: unhealthy Condition: seasonal allergic rhinitis Age Group: 19 - 34 yars Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/365920
Dizziness	3 patients	50 mg 3 times / day multiple, oral Highest studied dose Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/365920	unhealthy, 19 - 34 yars n = 19 Health Status: unhealthy Condition: seasonal allergic rhinitis Age Group: 19 - 34 yars Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/365920
Irritability	7 patients	50 mg 3 times / day multiple, oral Highest studied dose Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/365920	unhealthy, 19 - 34 yars n = 19 Health Status: unhealthy Condition: seasonal allergic rhinitis Age Group: 19 - 34 yars Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/365920

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		inhibitor 1702	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Nav1.5 93 Cav1.2 45 P-gp 1330	P-gp 1400

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1514	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/11290874/ Page: 5.0	likely
CYP2D6 1738	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	yes [Ki 4 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1400	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/12584158/ Page: 6.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 48	inhibitor 1489 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415947/
Nav1.5 96	inhibitor 1489 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415947/
hERG 1507	inhibitor 1489 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415947/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5818	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5818
ChemicalBook	CB2547530	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2547530
MolPort	MolPort-002-506-318	https://www.molport.com/shop/molecule-link/MolPort-002-506-318
eMolecules	1987151	https://www.emolecules.com/cgi-bin/more?vid=1987151

PubMed

Title	Date	PubMed
Cardiovascular action of hydroxyzine (atarax).	1956 Dec	13385806
Management of emotional disturbances; use of hydroxyzine (atarax) in general practice.	1958 Jun	13536863
Circulatory and respiratory effects of hydroxyzine in volunteers and geriatric patients.	1968 Jul-Aug	5690527
Hydroxyzine hydrochloride: possible adverse cardiac interactions.	1975	4857
Hydroxyzine-associated tardive dyskinesia.	1982 Apr	7103423
Peripheral antihistamine and central sedative effects of three H1-receptor antagonists.	1985	2864258
A comparison of acrivastine versus hydroxyzine and placebo in the treatment of chronic idiopathic urticaria.	1989	2569996
Prolongation of simple and choice reaction times in a double-blind comparison of twice-daily hydroxyzine versus terfenadine.	1989 Sep	2570798
Direct measurement of daytime sleepiness after administration of cetirizine and hydroxyzine with a standardized electroencephalographic assessment.	1990 Dec	2148177
Controlled trial of H1 antagonists in the treatment of chronic idiopathic urticaria.	1991 Oct	1683191
Prolonged penile erections induced by hydroxyzine: possible mechanism of action.	1994	7969858
Inhibition of mediator release in RBL-2H3 cells by some H1-antagonist derived anti-allergic drugs: relation to lipophilicity and membrane effects.	1995 Feb	7655991
[Modification of cognitive functions by 2 anxiolytic treatments in patients suffering from generalized anxiety].	1995 Mar-Apr	7781586
Hydroxyzine inhibits neurogenic bladder mast cell activation.	1998 Oct	9839659
Cetirizine-induce cholestasis.	2000 Oct	11034010
Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194).	2002 Feb	11809864
[Pruritus without skin manifestation--what kind of state of the art nursing intervention?].	2003 Oct	14619217
P-glycoprotein influences the brain concentrations of cetirizine (Zyrtec), a second-generation non-sedating antihistamine.	2003 Oct	14502547
Hydroxyzine-induced supraventricular tachycardia in a nine-year-old child.	2004 Feb	14985850
Psoriasis vulgaris flare during efalizumab therapy does not preclude future use: a case series.	2005 Aug 18	16109173
[A case of catatonia associated with the ingestion of hydroxyzine].	2005 Jan	15782600
Case studies: Use of salicylic acid (Avosil) and hydrogel (Avogel) in limiting scar formation.	2005 Mar 28	16921411
[Preoperative psychopharmacological correction in women with focal breast diseases].	2005 May-Jun	16076055
Neonatal seizures associated with maternal hydroxyzine hydrochloride in late pregnancy.	2005 Nov-Dec	16199350
Free radical oxidation in rat brain during chronic stress and pharmacological regulation of this process.	2005 Oct	16671569
[The use of atarax in the treatment of tic hyperkinesia in children: a pilot study].	2006	17117677
Skin reaction to hydroxyzine (Atarax): patch test utility.	2006 Apr	16650100
[The use of atarax in the treatment of attention deficit syndrome with hyperactivity and anxiety].	2007	18693347
[Use of anxiolytic atarax as a substitutive drug for benzodiazepine tranquilizers].	2007	18379511
Depressive symptoms in urticaria patients treated with first- or second-generation histamine 1 receptor antagonists.	2007 Aug	17632232
Hydroxyzine, a first generation H(1)-receptor antagonist, inhibits human ether-a-go-go-related gene (HERG) current and causes syncope in a patient with the HERG mutation.	2008 Dec	19057127
Development of a voltammetric procedure for assay of the antihistamine drug hydroxyzine at a glassy carbon electrode: Quantification and pharmacokinetic studies.	2008 Jan 15	18371719
Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study.	2009	19549290
Pharmacologic attenuation of pelvic pain in a murine model of interstitial cystitis.	2009 Nov 12	19909543
Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.	2010	19672097
[Comparative characteristics of hydroxyzine (atarax) and diazepam in the premedication regimen in children in dental practice].	2010 Jan-Feb	20564935
Chorea induced by antihistamine drugs.	2010 Mar 15	20108362
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013 Sep 5	23769903
Selective inhibition of hepatitis C virus infection by hydroxyzine and benztropine.	2014 Jun	24709263

Patents

Sample Use Guides

In Vivo Use Guide

For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested: in adults, 50-100 mg q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50-100 mg daily in divided doses. For use in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses, and in histamine-mediated pruritus: in adults, 25 mg t.i.d. or q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50-100 mg daily in divided doses. As a sedative when used as a premedication and following general anesthesia: 50-100 mg in adults, and 0.6 mg/kg in children.

Route of Administration: Oral

In Vitro Use Guide

Hydroxyzine reduced carbachol-induced serotonin release by 25% at 10(-6) M and 34% at 10(-5) M in rat bladder mast cells

Name

Type

Language

HYDROXYZINE

Official Name

English

HYDROXYZINE [WHO-DD]

Common Name

English

(+/-)-2-(2-(4-(P-CHLORO-.ALPHA.-PHENYLBENZYL)-1-PIPERAZINYL)ETHOXY)ETHANOL

Common Name

English

MAREX

Brand Name

English

U.C.B-4492

Brand Name

English

HYDROXYZINE [MI]

Common Name

English

ETHANOL, 2-(2-(4-(4-CHLORO-.ALPHA.-PHENYLBENZYL)-1-PIPERAZINYL)ETHOXY)-

Systematic Name

English

(+/-)-HYDROXYZINE

Common Name

English

HYDROXYZINE [MART.]

Common Name

English

HYDROXYZINE [VANDF]

Common Name

English

ETHANOL, 2-(2-(4-((4-CHLOROPHENYL)PHENYLMETHYL)-1-PIPERAZINYL)ETHOXY)-

Systematic Name

English

2-(2-(4-(P-CHLORO-.ALPHA.-PHENYLBENZYL)-1-PIPERAZINYL)ETHOXY)ETHANOL

Common Name

English

HYDROXYZINE [HSDB]

Common Name

English

ETHANOL, 2-(2-(4-((4-CHLOROPHENYL)PHENYLMETHYL)-1-PIPERAZINYL)ETHOXY)-,(+/-)-

Common Name

English

TRANQUIZINE

Brand Name

English

1-(P-CHLORO-.ALPHA.-PHENYLBENZYL)-4-(2-((2-HYDROXYETHOXY)ETHYL))PIPERAZINE

Common Name

English

1-(P-CHLOROBENZHYDRYL)-4-(2-(2-HYDROXYETHOXY)ETHYL)DIETHYLENEDIAMINE

Common Name

English

ATARAXOID

Brand Name

English

2-(2-(4-((4-CHLOROPHENYL)PHENYLMETHYL)-1-PIPERAZINYL)ETHOXY)ETHANOL

Systematic Name

English

NSC-169188

Code

English

HYDROXYZINE [INN]

Common Name

English

TRAN-Q

Brand Name

English

Classification Tree Code System Code

LIVERTOX

492