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Identification
Name Hydroxyzine
Accession Number DB00557 (APRD00688)
Type small molecule
Groups approved
Description

A 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. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Hidroxizina [INN-Spanish]
  • Hydroksyzyny [Polish]
  • Hydroxine
  • Hydroxizine
  • Hydroxizinum
  • Hydroxycine
  • Hydroxyzin
  • Hydroxyzine Base
  • Hydroxyzine Hcl
  • Hydroxyzine Pamoate
  • Hydroxyzinum [INN-Latin]
  • Hydroxyzyne
  • Idrossizina [Dcit]
Brand names
  • Alamon
  • Atara
  • Atarax
  • Ataraxoid
  • Atarazoid
  • Atarox
  • Atazina
  • Aterax
  • Deinait
  • Durrax
  • Equipoise
  • Equipose
  • Fenarol
  • Hy-Pam 25
  • Hychotine
  • Masmoran
  • Neo-Calma
  • Neurozina
  • Nevrolaks
  • Orgatrax
  • Pamazone
  • Paxistil
  • Placidol
  • Plaxidol
  • Quiess
  • Tran-Q
  • Tranquizine
  • Traquizine
  • Vesparaz-Wirkstoff
  • Vistaril
  • Vistaril Pamoate
  • Vistazine
Brand name mixtures Not Available
Categories
  • Antipruritics
  • Histamine H1 Antagonists
  • Anxiolytics sedatives and hypnotics
CAS number 68-88-2
Weight Average: 374.904
Monoisotopic: 374.176105825
Chemical Formula C21H27ClN2O2
InChI Key InChIKey=ZQDWXGKKHFNSQK-UHFFFAOYSA-N
InChI
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
Plain Text
IUPAC Name
2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)ethan-1-ol
SMILES
OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Diphenylmethanes
Substructures
  • Hydroxy Compounds
  • Piperazines
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Alcohols and Polyols
  • Aliphatic and Aryl Amines
  • Diphenylmethanes
  • Heterocyclic compounds
  • Aromatic compounds
Pharmacology
Indication 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.
Pharmacodynamics 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's active metabolite, cetirizine, is also used as an H1-antagonist.
Mechanism of action 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.
Absorption Rapidly absorbed from the gastrointestinal tract
Volume of distribution Not Available
Protein binding 93%
Metabolism

Hepatic
Route of elimination Not Available
Half life 20 to 25 hours
Clearance Not Available
Toxicity Oral, rat LD50: 950 mg/kg. Symptoms of overexposure include hypersedation.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Altana inc
  • App pharmaceuticals llc
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Pharmafair inc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Solopak laboratories inc
  • Watson laboratories inc
  • Wyeth ayerst laboratories
  • Organon usa inc
  • Pfizer laboratories div pfizer inc
  • Roerig div pfizer inc
  • Actavis mid atlantic llc
  • Alpharma us pharmaceuticals division
  • Hi tech pharmacal co inc
  • Kv pharmaceutical co
  • Vintage pharmaceuticals inc
  • Wockhardt eu operations (swiss) ag
  • Pfizer inc
  • Able laboratories inc
  • Actavis totowa llc
  • Amneal pharmaceutical
  • Halsey drug co inc
  • Heritage pharmaceuticals inc
  • Hetero drugs ltd unit iii
  • Invagen pharmaceuticals inc
  • Ivax pharmaceuticals inc
  • Kvk tech inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Northstar healthcare holdings ltd
  • Pliva inc
  • Purepac pharmaceutical co
  • Quantum pharmics ltd
  • Sandoz inc
  • Sun pharmaceutical industries inc
  • Superpharm corp
  • Usl pharma inc
  • Vintage pharmaceuticals llc
  • Barr laboratories inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Par pharmaceutical inc
  • Vangard laboratories inc div midway medical co
  • Teva pharmaceuticals usa inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Liquid Intramuscular
Syrup Oral
Prices
Unit description Cost Unit
Hydroxyzine Hcl 50 mg/ml 4.42 USD ml
Hydroxyzine 50 mg/ml vial 3.96 USD ml
Hydroxyzine 25 mg/ml vial 3.6 USD ml
Hydroxyzine hcl powder 2.75 USD g
Hydroxyzine pamoate powder 2.14 USD g
Vistaril 50 mg capsule 2.03 USD capsule
HydrOXYzine HCl 50 mg/ml vial 1.78 USD vial
Vistaril 25 mg capsule 1.71 USD capsule
Vistaril 100 mg capsule 1.7 USD capsule
Hydroxyzine hcl 50 mg tablet 1.19 USD tablet
Hydroxyzine hcl 10 mg tablet 0.72 USD tablet
Hydroxyzine hcl 25 mg tablet 0.7 USD tablet
HydrOXYzine Pamoate 100 mg capsule 0.67 USD capsule
Hydroxyzine pam 50 mg capsule 0.64 USD capsule
Hydroxyzine pam 100 mg capsule 0.63 USD capsule
Hydroxyzine pam 25 mg capsule 0.46 USD capsule
Vistaril 25 mg/5ml Suspension 0.45 USD ml
HydrOXYzine Pamoate 25 mg capsule 0.3 USD capsule
HydrOXYzine Pamoate 50 mg capsule 0.23 USD capsule
Apo-Hydroxyzine 50 mg Capsule 0.22 USD capsule
Novo-Hydroxyzin 50 mg Capsule 0.22 USD capsule
Apo-Hydroxyzine 25 mg Capsule 0.15 USD capsule
Novo-Hydroxyzin 25 mg Capsule 0.15 USD capsule
HydrOXYzine HCl 10 mg/5ml Syrup 0.13 USD ml
Apo-Hydroxyzine 10 mg Capsule 0.12 USD capsule
Novo-Hydroxyzin 10 mg Capsule 0.12 USD capsule
Atarax 2 mg/ml Syrup 0.06 USD ml
Pms-Hydroxyzine 2 mg/ml Syrup 0.04 USD ml
Patents Not Available
Properties
State solid
Melting point 190 oC
Experimental Properties
Property Value Source
water solubility < 700 mg/mL PhysProp
logP 2.7 PhysProp
Predicted Properties
Property Value Source
water solubility 9.14e-02 g/l ALOGPS
logP 3.43 ALOGPS
logP 3.41 ChemAxon Molconvert
logS -3.61 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 35.94 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 107.07 ChemAxon Molconvert
polarizability 41.99 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. HUTCHEON DE, MORRIS DL, SCRIABINE A: Cardiovascular action of hydroxyzine (atarax). J Pharmacol Exp Ther. 1956 Dec;118(4):451-60. Pubmed
  2. DOLAN CM: Management of emotional disturbances; use of hydroxyzine (atarax) in general practice. Calif Med. 1958 Jun;88(6):443-4. Pubmed
  3. Clark BG, Araki M, Brown HW: Hydroxyzine-associated tardive dyskinesia. Ann Neurol. 1982 Apr;11(4):435. Pubmed
External Links
Resource Link
KEGG Compound C07045 Link_out
PubChem Compound 3658 Link_out
PubChem Substance 46508556 Link_out
ChemSpider 3531 Link_out
BindingDB 22875 Link_out
ChEBI 5818 Link_out
ChEMBL 5818 Link_out
Therapeutic Targets Database DAP000324 Link_out
PharmGKB PA449943 Link_out
Drug Product Database 739618 Link_out
RxList http://www.rxlist.com/cgi/generic/hydrox.htm Link_out
Drugs.com http://www.drugs.com/hydroxyzine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ata1035.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Hydroxyzine Link_out
ATC Codes
  • N05BB01
AHFS Codes
  • 28:24.92
PDB Entries Not Available
FDA label Not Available
MSDS show (73.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take with food.
Targets

1. Histamine H1 receptor

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P35367 Link_out
Gene: HRH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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. Pubmed
  3. 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. Pubmed
  4. Chen C: Physicochemical, pharmacological and pharmacokinetic properties of the zwitterionic antihistamines cetirizine and levocetirizine. Curr Med Chem. 2008;15(21):2173-91. Pubmed
  5. Snowman AM, Snyder SH: Cetirizine: actions on neurotransmitter receptors. J Allergy Clin Immunol. 1990 Dec;86(6 Pt 2):1025-8. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hamelin BA, Bouayad A, Drolet B, Gravel A, Turgeon J: In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists. Drug Metab Dispos. 1998 Jun;26(6):536-9. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.