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

Details

Stereochemistry RACEMIC
Molecular Formula C23H16O6.C21H27ClN2O2
Molecular Weight 763.274
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HYDROXYZINE PAMOATE

SMILES

OCCOCCN1CCN(CC1)C(C2=CC=CC=C2)C3=CC=C(Cl)C=C3.OC(=O)C4=CC5=C(C=CC=C5)C(CC6=C7C=CC=CC7=CC(C(O)=O)=C6O)=C4O

InChI

InChIKey=ASDOKGIIKXGMNB-UHFFFAOYSA-N
InChI=1S/C23H16O6.C21H27ClN2O2/c24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29;22-20-8-6-19(7-9-20)21(18-4-2-1-3-5-18)24-12-10-23(11-13-24)14-16-26-17-15-25/h1-10,24-25H,11H2,(H,26,27)(H,28,29);1-9,21,25H,10-17H2

HIDE SMILES / InChI

Molecular Formula C23H16O6
Molecular Weight 388.3695
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
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

7.8589441E11
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

7.8589441E11
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
Hydroxyzine hydrochloride: possible adverse cardiac interactions.
1975
Peripheral antihistamine and central sedative effects of three H1-receptor antagonists.
1985
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
Hydroxyzine-induced supraventricular tachycardia in a nine-year-old child.
2004 Feb
Psoriasis vulgaris flare during efalizumab therapy does not preclude future use: a case series.
2005 Aug 18
Skin reaction to hydroxyzine (Atarax): patch test utility.
2006 Apr
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
Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.
2010
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
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.
2013 Sep 5
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 Fri Dec 15 16:17:59 UTC 2023
Edited
by admin
on Fri Dec 15 16:17:59 UTC 2023
Record UNII
M20215MUFR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
HYDROXYZINE PAMOATE
MI   ORANGE BOOK   USP   USP-RS   VANDF  
Common Name English
HYDROXYZINE EMBONATE [MART.]
Common Name English
HYDROXYZINE EMBONATE
MART.   WHO-DD  
Common Name English
HYDROXYZINE PAMOATE [USP MONOGRAPH]
Common Name English
HYDROXYZINE PAMOATE [VANDF]
Common Name English
HYDROXYZINE PAMOATE [MI]
Common Name English
NSC-757063
Code English
(±)-2-(2-(4-(P-CHLORO-.ALPHA.-PHENYLBENZYL)-1-PIPERAZINYL)ETHOXY)ETHANOL 4,4'-METHYLENEBIS(3-HYDROXY-2-NAPHTHOATE) (1:1)
Common Name English
HYDROXYZINE PAMOATE [USP-RS]
Common Name English
Hydroxyzine embonate [WHO-DD]
Common Name English
HYDROXYZINE PAMOATE [ORANGE BOOK]
Common Name English
HY-PAM
Brand Name English
HYDROXYZINE PAMOATE [JAN]
Common Name English
ETHANOL, 2-(2-(4-((4-CHLOROPHENYL)PHENYLMETHYL)-1-PIPERAZINYL)ETHOXY)-, (±)-, COMPD. WITH 4,4'-METHYLENEBIS(3-HYDROXY-2-NAPHTHALENECARBOXYLIC ACID) (1:1)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29578
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
Code System Code Type Description
NSC
757063
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
RS_ITEM_NUM
1334006
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
MERCK INDEX
m6159
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY Merck Index
EPA CompTox
DTXSID00907580
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
EVMPD
SUB02597MIG
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
RXCUI
203182
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY RxNorm
SMS_ID
100000085225
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
FDA UNII
M20215MUFR
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
ChEMBL
CHEMBL896
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
NCI_THESAURUS
C47560
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
CAS
10246-75-0
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
PUBCHEM
25096
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
DAILYMED
M20215MUFR
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
DRUG BANK
DBSALT000984
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
ECHA (EC/EINECS)
233-582-1
Created by admin on Fri Dec 15 16:17:59 UTC 2023 , Edited by admin on Fri Dec 15 16:17:59 UTC 2023
PRIMARY
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PARENT -> SALT/SOLVATE
SALT/SOLVATE -> SALT/SOLVATE
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CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
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ACTIVE MOIETY