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
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
A comparison of acrivastine versus hydroxyzine and placebo in the treatment of chronic idiopathic urticaria.
1989
Prolongation of simple and choice reaction times in a double-blind comparison of twice-daily hydroxyzine versus terfenadine.
1989 Sep
Direct measurement of daytime sleepiness after administration of cetirizine and hydroxyzine with a standardized electroencephalographic assessment.
1990 Dec
Prolonged penile erections induced by hydroxyzine: possible mechanism of action.
1994
Inhibition of mediator release in RBL-2H3 cells by some H1-antagonist derived anti-allergic drugs: relation to lipophilicity and membrane effects.
1995 Feb
[Modification of cognitive functions by 2 anxiolytic treatments in patients suffering from generalized anxiety].
1995 Mar-Apr
Hydroxyzine inhibits neurogenic bladder mast cell activation.
1998 Oct
Cetirizine-induce cholestasis.
2000 Oct
[Pruritus without skin manifestation--what kind of state of the art nursing intervention?].
2003 Oct
Psoriasis vulgaris flare during efalizumab therapy does not preclude future use: a case series.
2005 Aug 18
[Preoperative psychopharmacological correction in women with focal breast diseases].
2005 May-Jun
Neonatal seizures associated with maternal hydroxyzine hydrochloride in late pregnancy.
2005 Nov-Dec
[The use of atarax in the treatment of tic hyperkinesia in children: a pilot study].
2006
Skin reaction to hydroxyzine (Atarax): patch test utility.
2006 Apr
[The use of atarax in the treatment of attention deficit syndrome with hyperactivity and anxiety].
2007
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
Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study.
2009
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.
2013 Sep 5
Selective inhibition of hepatitis C virus infection by hydroxyzine and benztropine.
2014 Jun
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 02:00:32 GMT 2023
Edited
by admin
on Sat Dec 16 02:00:32 GMT 2023
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, (-)-
Systematic Name English
Code System Code Type Description
CAS
163837-37-4
Created by admin on Sat Dec 16 02:00:32 GMT 2023 , Edited by admin on Sat Dec 16 02:00:32 GMT 2023
PRIMARY
FDA UNII
5AQ4KXB9U4
Created by admin on Sat Dec 16 02:00:32 GMT 2023 , Edited by admin on Sat Dec 16 02:00:32 GMT 2023
PRIMARY
Related Record Type Details
ENANTIOMER -> ENANTIOMER
RACEMATE -> ENANTIOMER