HYDROXYZINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H27ClN2O2
Molecular Weight	374.904
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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
Leishmania (L.) infantum promastigotes viability 6 Target ID: Leishmania (L.) infantum promastigotes viability Sources: https://www.ncbi.nlm.nih.gov/pubmed/24905294	Inhibitor 8297	59.57 µM [IC50]
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: http://www.drugbank.ca/drugs/DB00557	Antagonist 2778
Monoamine oxidase B 72 Target ID: CHEMBL2993 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17447421	Inhibitor 8297	38.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 267 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048,011795s025lbl.pdf	Palliative		Approved 8429	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 29 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048,011795s025lbl.pdf	Palliative		Approved 8429	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 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Nav1.5 97 Cav1.2 45 P-gp 1461	P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11290874/ Page: 5.0	likely
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	yes [Ki 4 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12584158/ Page: 6.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 49	inhibitor 1626 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415947/
Nav1.5 100	inhibitor 1626 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415947/
hERG 1647	inhibitor 1626 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
Hydroxyzine-associated tardive dyskinesia.	1982 Apr	7103423
Direct measurement of daytime sleepiness after administration of cetirizine and hydroxyzine with a standardized electroencephalographic assessment.	1990 Dec	2148177
[Preoperative psychopharmacological correction in women with focal breast diseases].	2005 May-Jun	16076055
[The use of atarax in the treatment of tic hyperkinesia in children: a pilot study].	2006	17117677
[Comparative characteristics of hydroxyzine (atarax) and diazepam in the premedication regimen in children in dental practice].	2010 Jan-Feb	20564935
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

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

(±)-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

Hydroxyzine [WHO-DD]

Common 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

NBK548128