U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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, (+)-

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 C21H27ClN2O2
Molecular Weight 374.904
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Leishmania (L.) infantum promastigotes viability
59.57 µM [IC50]
38.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
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
Palliative
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
31.371 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
479.174 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
18.4 h
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
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
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

Doses

DosePopulationAdverse 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:
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:
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:
AEs

AEs

AESignificanceDosePopulation
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:
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:
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:
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:
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:
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:
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:
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:
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:
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:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
likely
yes [Ki 4 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Tox targets
PubMed

PubMed

TitleDatePubMed
Cardiovascular action of hydroxyzine (atarax).
1956 Dec
Management of emotional disturbances; use of hydroxyzine (atarax) in general practice.
1958 Jun
Circulatory and respiratory effects of hydroxyzine in volunteers and geriatric patients.
1968 Jul-Aug
Hydroxyzine hydrochloride: possible adverse cardiac interactions.
1975
Hydroxyzine-associated tardive dyskinesia.
1982 Apr
Inhibition of mediator release in RBL-2H3 cells by some H1-antagonist derived anti-allergic drugs: relation to lipophilicity and membrane effects.
1995 Feb
Hydroxyzine inhibits neurogenic bladder mast cell activation.
1998 Oct
Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194).
2002 Feb
[Pruritus without skin manifestation--what kind of state of the art nursing intervention?].
2003 Oct
P-glycoprotein influences the brain concentrations of cetirizine (Zyrtec), a second-generation non-sedating antihistamine.
2003 Oct
Hydroxyzine-induced supraventricular tachycardia in a nine-year-old child.
2004 Feb
[A case of catatonia associated with the ingestion of hydroxyzine].
2005 Jan
Free radical oxidation in rat brain during chronic stress and pharmacological regulation of this process.
2005 Oct
[The use of atarax in the treatment of tic hyperkinesia in children: a pilot study].
2006
[The use of atarax in the treatment of attention deficit syndrome with hyperactivity and anxiety].
2007
[Use of anxiolytic atarax as a substitutive drug for benzodiazepine tranquilizers].
2007
Depressive symptoms in urticaria patients treated with first- or second-generation histamine 1 receptor antagonists.
2007 Aug
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
Development of a voltammetric procedure for assay of the antihistamine drug hydroxyzine at a glassy carbon electrode: Quantification and pharmacokinetic studies.
2008 Jan 15
Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study.
2009
Pharmacologic attenuation of pelvic pain in a murine model of interstitial cystitis.
2009 Nov 12
Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.
2010
[Comparative characteristics of hydroxyzine (atarax) and diazepam in the premedication regimen in children in dental practice].
2010 Jan-Feb
Chorea induced by antihistamine drugs.
2010 Mar 15
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Sample Use Guides

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 Sat Dec 16 02:02:04 GMT 2023
Edited
by admin
on Sat Dec 16 02:02:04 GMT 2023
Record UNII
GF8H55RPZ9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
HYDROXYZINE DIHYDROCHLORIDE, (+)-
Common Name English
ETHANOL, 2-(2-(4-((4-CHLOROPHENYL)PHENYLMETHYL)-1-PIPERAZINYL)ETHOXY)-, DIHYDROCHLORIDE, (+)-
Systematic Name English
Code System Code Type Description
CAS
163837-38-5
Created by admin on Sat Dec 16 02:02:04 GMT 2023 , Edited by admin on Sat Dec 16 02:02:04 GMT 2023
PRIMARY
PUBCHEM
91513
Created by admin on Sat Dec 16 02:02:04 GMT 2023 , Edited by admin on Sat Dec 16 02:02:04 GMT 2023
PRIMARY
FDA UNII
GF8H55RPZ9
Created by admin on Sat Dec 16 02:02:04 GMT 2023 , Edited by admin on Sat Dec 16 02:02:04 GMT 2023
PRIMARY
Related Record Type Details
RACEMATE -> ENANTIOMER
ENANTIOMER -> ENANTIOMER