HYDROXYZINE DIHYDROCHLORIDE, (-)-

Details

Stereochemistry	UNKNOWN
Molecular Formula	C21H27ClN2O2.2ClH
Molecular Weight	447.826
Optical Activity	( - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of HYDROXYZINE DIHYDROCHLORIDE, (-)-

Structure Search

SMILES

Cl.Cl.OCCOCCN1CCN(CC1)C(C2=CC=CC=C2)C3=CC=C(Cl)C=C3

InChI

InChIKey=ANOMHKZSQFYSBR-UHFFFAOYSA-N

InChI=1S/C21H27ClN2O2.2ClH/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;2*1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C21H27ClN2O2
Molecular Weight	374.904
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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
Leishmania (L.) infantum promastigotes viability 6 Target ID: Leishmania (L.) infantum promastigotes viability Sources: https://www.ncbi.nlm.nih.gov/pubmed/24905294	Inhibitor 8504	59.57 µM [IC50]
Histamine H1 receptor 316 Target ID: CHEMBL231 Sources: http://www.drugbank.ca/drugs/DB00557	Antagonist 2849
Monoamine oxidase B 75 Target ID: CHEMBL2993 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17447421	Inhibitor 8504	38.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 275 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048,011795s025lbl.pdf	Palliative		Approved 8583	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 1994
Pruritus 31 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048,011795s025lbl.pdf	Palliative		Approved 8583	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 1994

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://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
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

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://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
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

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 Health Status: unhealthy Age Group: 19 - 34 yars Sex: M+F 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 Health Status: unhealthy Age Group: 19 - 34 yars Sex: M+F 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 Health Status: unhealthy Age Group: 19 - 34 yars Sex: M+F 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 Health Status: unhealthy Age Group: 19 - 34 yars Sex: M+F 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 Health Status: unhealthy Age Group: 19 - 34 yars Sex: M+F 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 Health Status: unhealthy Age Group: 19 - 34 yars Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/365920

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Nav1.5 116 Cav1.2 58 P-gp 1741	P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11290874/ Page: 5.0	likely
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	yes [Ki 4 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12584158/ Page: 6.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 63	inhibitor 2237 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415947/
Nav1.5 119	inhibitor 2237 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415947/
hERG 2263	inhibitor 2237 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
eMolecules	1987151	https://www.emolecules.com/cgi-bin/more?vid=1987151
MolPort	MolPort-002-506-318	https://www.molport.com/shop/molecule-link/MolPort-002-506-318

PubMed

Title	Date	PubMed
Selective inhibition of hepatitis C virus infection by hydroxyzine and benztropine.	2014-06	24709263
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013-09-05	23769903
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011-07-14	21599003
[Comparative characteristics of hydroxyzine (atarax) and diazepam in the premedication regimen in children in dental practice].	2010-06-23	20564935
Chorea induced by antihistamine drugs.	2010-03-15	20108362
Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.	2010	19672097
Pharmacologic attenuation of pelvic pain in a murine model of interstitial cystitis.	2009-11-12	19909543
Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study.	2009	19549290
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.	2008-12	19057127
Development of a voltammetric procedure for assay of the antihistamine drug hydroxyzine at a glassy carbon electrode: Quantification and pharmacokinetic studies.	2008-01-15	18371719
Depressive symptoms in urticaria patients treated with first- or second-generation histamine 1 receptor antagonists.	2007-08	17632232
[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
Skin reaction to hydroxyzine (Atarax): patch test utility.	2006-04	16650100
[The use of atarax in the treatment of tic hyperkinesia in children: a pilot study].	2006	17117677
Free radical oxidation in rat brain during chronic stress and pharmacological regulation of this process.	2005-10	16671569
Psoriasis vulgaris flare during efalizumab therapy does not preclude future use: a case series.	2005-08-18	16109173
[Preoperative psychopharmacological correction in women with focal breast diseases].	2005-08-04	16076055
Case studies: Use of salicylic acid (Avosil) and hydrogel (Avogel) in limiting scar formation.	2005-03-28	16921411
[A case of catatonia associated with the ingestion of hydroxyzine].	2005-01	15782600
Neonatal seizures associated with maternal hydroxyzine hydrochloride in late pregnancy.	2004-11-16	16199350
Hydroxyzine-induced supraventricular tachycardia in a nine-year-old child.	2004-02	14985850
[Pruritus without skin manifestation--what kind of state of the art nursing intervention?].	2003-10	14619217
P-glycoprotein influences the brain concentrations of cetirizine (Zyrtec), a second-generation non-sedating antihistamine.	2003-10	14502547
Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194).	2002-02	11809864
Cetirizine-induce cholestasis.	2000-10	11034010
Hydroxyzine inhibits neurogenic bladder mast cell activation.	1998-10	9839659
[Modification of cognitive functions by 2 anxiolytic treatments in patients suffering from generalized anxiety].	1995-03-01	7781586
Inhibition of mediator release in RBL-2H3 cells by some H1-antagonist derived anti-allergic drugs: relation to lipophilicity and membrane effects.	1995-02	7655991
Prolonged penile erections induced by hydroxyzine: possible mechanism of action.	1994	7969858
Controlled trial of H1 antagonists in the treatment of chronic idiopathic urticaria.	1991-10	1683191
Direct measurement of daytime sleepiness after administration of cetirizine and hydroxyzine with a standardized electroencephalographic assessment.	1990-12	2148177
Prolongation of simple and choice reaction times in a double-blind comparison of twice-daily hydroxyzine versus terfenadine.	1989-09	2570798
A comparison of acrivastine versus hydroxyzine and placebo in the treatment of chronic idiopathic urticaria.	1989	2569996
Peripheral antihistamine and central sedative effects of three H1-receptor antagonists.	1985	2864258
Hydroxyzine-associated tardive dyskinesia.	1982-04	7103423
Hydroxyzine hydrochloride: possible adverse cardiac interactions.	1975	4857
Circulatory and respiratory effects of hydroxyzine in volunteers and geriatric patients.	1968-07-01	5690527
Management of emotional disturbances; use of hydroxyzine (atarax) in general practice.	1958-06	13536863
Cardiovascular action of hydroxyzine (atarax).	1956-12	13385806

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

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:06:20 GMT 2025` Edited by `admin` on `Mon Mar 31 21:06:20 GMT 2025`
Record UNII	5AQ4KXB9U4
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HYDROXYZINE DIHYDROCHLORIDE, (-)-

Common Name

English

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

Preferred Name

English

Code System Code Type Description

CAS

163837-37-4

Created by admin on Mon Mar 31 21:06:20 GMT 2025 , Edited by admin on Mon Mar 31 21:06:20 GMT 2025

PRIMARY

FDA UNII

5AQ4KXB9U4

Created by admin on Mon Mar 31 21:06:20 GMT 2025 , Edited by admin on Mon Mar 31 21:06:20 GMT 2025

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HYDROXYZINE DIHYDROCHLORIDE, (+)-

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RACEMATE -> ENANTIOMER