You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-21 20:27:08 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2823
Identification
Common NameHydroxyzine
ClassSmall Molecule
DescriptionA histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative.
Compound Type
  • Amine
  • Antipruritic
  • Anxiolytic
  • Drug
  • Ether
  • Histamine H1 Antagonist
  • Hypnotic and Sedative
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Atarax
Hidroxizina
Hychotine
Hydroksyzyny
Hydroxine
Hydroxizine
Hydroxizinum
Hydroxycine
Hydroxyzin
Hydroxyzine Base
Hydroxyzine Pamoate
Hydroxyzinum
Hydroxyzyne
Hyzine
Idrossizina
Masmoran
Rezine
Vistaject-50
Vistaril
Vistazine
Chemical FormulaC21H27ClN2O2
Average Molecular Mass374.904 g/mol
Monoisotopic Mass374.176 g/mol
CAS Registry Number68-88-2
IUPAC Name2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)ethan-1-ol
Traditional Namehydroxyzine
SMILESOCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1
InChI IdentifierInChI=1/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
InChI KeyInChIKey=ZQDWXGKKHFNSQK-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Chlorobenzene
  • Aralkylamine
  • Halobenzene
  • N-alkylpiperazine
  • Aryl chloride
  • Aryl halide
  • 1,4-diazinane
  • Piperazine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Dialkyl ether
  • Azacycle
  • Ether
  • Organoheterocyclic compound
  • Organohalogen compound
  • Organic nitrogen compound
  • Amine
  • Hydrocarbon derivative
  • Alcohol
  • Organopnictogen compound
  • Organic oxygen compound
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Primary alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point193°C
Boiling PointNot Available
Solubility< 700 mg/mL
LogP2.7
Predicted Properties
PropertyValueSource
Water Solubility0.091 g/LALOGPS
logP3.43ALOGPS
logP3.41ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)15.12ChemAxon
pKa (Strongest Basic)7.82ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area35.94 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity107.07 m³·mol⁻¹ChemAxon
Polarizability41.99 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-6491000000-95c46c16c2b29900f4d9JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-6491000000-95c46c16c2b29900f4d9JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udj-4291000000-5750700bc5e75e581102JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0udr-6589100000-8c29584ceed777207042JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0udi-0593000000-f20d2328497a3a80239bJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0019000000-f6d89e75a6d7e8af9001JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0w4i-3179000000-af704769cca5c3dc8e6eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udj-5292000000-d581a3d2a57e2fa067fdJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-1009000000-753db826ff35e907de51JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-2029000000-b8ad29be99c096f6967aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01ox-9061000000-5b2e7de6b58b52c40177JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0uxr-4591000000-d2e3424c44feae8a5d9cJSpectraViewer | MoNA
Toxicity Profile
Route of ExposureOral, Intramuscular. Rapidly absorbed from the gastrointestinal tract
Mechanism of ToxicityHydroxyzine 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.
MetabolismHepatic Half Life: 20 to 25 hours
Toxicity ValuesOral, rat LD50: 950 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overexposure include hypersedation.
TreatmentIf vomiting has not occurred spontaneously, it should be induced. Immediate gastric lavage is also recommended. General supportive care, including frequent monitoring of the vital signs and close observation of the patient, is indicated. Hypotension, though unlikely, may be controlled with intravenous fluids and norepinephrine or metaraminol. Do not use epinephrine as hydroxyzine hydrochloride counteracts its pressor action. There is no specific antidote. It is doubtful that hemodialysis would be of any value in the treatment of overdosage with hydroxyzine. However, if other agents such as barbiturates have been ingested concomitantly, hemodialysis may be indicated. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00557
HMDB IDHMDB14697
PubChem Compound ID3658
ChEMBL IDCHEMBL896
ChemSpider ID3531
KEGG IDC07045
UniProt IDNot Available
OMIM ID
ChEBI ID5818
BioCyc IDNot Available
CTD IDNot Available
Stitch IDHydroxyzine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkHydroxyzine
References
Synthesis Reference

U.S. Patent 2,899,436.

MSDSLink
General References
  1. HUTCHEON DE, MORRIS DL, SCRIABINE A: Cardiovascular action of hydroxyzine (atarax). J Pharmacol Exp Ther. 1956 Dec;118(4):451-60. [13385806 ]
  2. DOLAN CM: Management of emotional disturbances; use of hydroxyzine (atarax) in general practice. Calif Med. 1958 Jun;88(6):443-4. [13536863 ]
  3. Clark BG, Araki M, Brown HW: Hydroxyzine-associated tardive dyskinesia. Ann Neurol. 1982 Apr;11(4):435. [7103423 ]
  4. Drugs.com [Link]
  5. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.001 uMNot AvailableBindingDB 22875
Inhibitory0.002 uMNot AvailableBindingDB 22875
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Spahr L, Coeytaux A, Giostra E, Hadengue A, Annoni JM: Histamine H1 blocker hydroxyzine improves sleep in patients with cirrhosis and minimal hepatic encephalopathy: a randomized controlled pilot trial. Am J Gastroenterol. 2007 Apr;102(4):744-53. Epub 2007 Jan 11. [17222324 ]
  3. Gillard M, Van Der Perren C, Moguilevsky N, Massingham R, Chatelain P: Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194). Mol Pharmacol. 2002 Feb;61(2):391-9. [11809864 ]
  4. Sakaguchi T, Itoh H, Ding WG, Tsuji K, Nagaoka I, Oka Y, Ashihara T, Ito M, Yumoto Y, Zenda N, Higashi Y, Takeyama Y, Matsuura H, Horie M: 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. J Pharmacol Sci. 2008 Dec;108(4):462-71. Epub 2008 Dec 5. [19057127 ]
  5. Levander S, Hagermark O, Stahle M: Peripheral antihistamine and central sedative effects of three H1-receptor antagonists. Eur J Clin Pharmacol. 1985;28(5):523-9. [2864258 ]
General Function:
Histamine receptor activity
Specific Function:
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
Gene Name:
HRH4
Uniprot ID:
Q9H3N8
Molecular Weight:
44495.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 22875
References
  1. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R: Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther. 2005 Sep;314(3):1310-21. Epub 2005 Jun 9. [15947036 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.45 uMNot AvailableBindingDB 22875
IC500.813 uMNot AvailableBindingDB 22875
References
  1. De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP: Structure-based identification of OATP1B1/3 inhibitors. Mol Pharmacol. 2013 Jun;83(6):1257-67. doi: 10.1124/mol.112.084152. Epub 2013 Apr 9. [23571415 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.94 uMNot AvailableBindingDB 22875
IC501.23 uMNot AvailableBindingDB 22875
References
  1. De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP: Structure-based identification of OATP1B1/3 inhibitors. Mol Pharmacol. 2013 Jun;83(6):1257-67. doi: 10.1124/mol.112.084152. Epub 2013 Apr 9. [23571415 ]