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Identification
Name Guanabenz
Accession Number DB00629 (APRD00487)
Type small molecule
Groups approved
Description

An alpha-2 selective adrenergic agonist used as an antihypertensive agent. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • GBZ
  • Guanabenz [USAN:INN]
  • Guanabenz Acetate
  • Guanabenz(USAN)
  • Guanabenzo [INN-Spanish]
  • Guanabenzum [INN-Latin]
  • Wy 8678 base
  • Wytensin
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • Sympatholytics
  • Adrenergic alpha-Agonists
CAS number 5051-62-7
Weight Average: 231.082
Monoisotopic: 230.012601690
Chemical Formula C8H8Cl2N4
InChI Key InChIKey=WDZVGELJXXEGPV-UHFFFAOYSA-N
InChI
InChI=1S/C8H8Cl2N4/c9-6-2-1-3-7(10)5(6)4-13-14-8(11)12/h1-4H,(H4,11,12,14)
Plain Text
IUPAC Name
2-{[(2,6-dichlorophenyl)methylidene]amino}guanidine
SMILES
NC(N)=NN=CC1=C(Cl)C=CC=C1Cl
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
  • Halobenzenes
Substructures
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Guanidines
  • Aromatic compounds
  • Carboxamidines
  • Hydrazine Derivatives
  • Imines
Pharmacology
Indication For management of High blood pressure
Pharmacodynamics Guanabenz, a centrally acting α-2 adrenergic agonist, is indicated for treatment of hypertension.
Mechanism of action Guanabenz's antihypertensive effect is thought to be due to central alpha-adrenergic stimulation, which results in a decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature in addition to a decreased systolic and diastolic blood pressure and a slight slowing of pulse rate. Chronic administration of guanabenz also causes a decrease in peripheral vascular resistance.
Absorption Approximately 75% absorbed from gastrointestinal tract
Volume of distribution Not Available
Protein binding 90%
Metabolism

Hepatic
Route of elimination Not Available
Half life 6 hours.
Clearance Not Available
Toxicity Excessive contraction of the pupils, irritability, low blood pressure, sleepiness, slow heartbeat, sluggishness
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
  • Wyeth ayerst laboratories
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
Guanabenz acetate 8 mg tablet 2.13 USD tablet
Guanabenz acetate 4 mg tablet 1.07 USD tablet
Patents Not Available
Properties
State solid
Melting point 228 oC
Experimental Properties
Property Value Source
logP 3.2 PhysProp
Caco2 permeability -4.5 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 8.89e-02 g/l ALOGPS
logP 2.25 ALOGPS
logP 1.71 ChemAxon Molconvert
logS -3.41 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 76.76 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 58.15 ChemAxon Molconvert
polarizability 21.58 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D04375 Link_out
KEGG Compound C07034 Link_out
PubChem Compound 5702063 Link_out
PubChem Substance 46505200 Link_out
ChemSpider 3397 Link_out
Therapeutic Targets Database DAP000232 Link_out
PharmGKB PA449819 Link_out
Drug Product Database 0 Link_out
Drugs.com http://www.drugs.com/cdi/guanabenz.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/gua1612.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Guanabenz Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (219.1 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Alpha-2A adrenergic receptor

Pharmacological action: yes
Actions: agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Piletz JE, Sletten K: Nonadrenergic imidazoline binding sites on human platelets. J Pharmacol Exp Ther. 1993 Dec;267(3):1493-502. Pubmed
  2. Bockman CS, Jeffries WB, Abel PW: Binding and functional characterization of alpha-2 adrenergic receptor subtypes on pig vascular endothelium. J Pharmacol Exp Ther. 1993 Dec;267(3):1126-33. Pubmed
  3. Bockman CS, Gonzalez-Cabrera I, Abel PW: Alpha-2 adrenoceptor subtype causing nitric oxide-mediated vascular relaxation in rats. J Pharmacol Exp Ther. 1996 Sep;278(3):1235-43. Pubmed
  4. Galeotti N, Bartolini A, Ghelardini C: Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype. Behav Brain Res. 2004 Aug 31;153(2):409-17. Pubmed
  5. van Zwieten PA: Centrally acting antihypertensives: a renaissance of interest. Mechanisms and haemodynamics. J Hypertens Suppl. 1997 Jan;15(1):S3-8. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  2. Clement B, Demesmaeker M: Formation of guanoxabenz from guanabenz in human liver. A new metabolic marker for CYP1A2. Drug Metab Dispos. 1997 Nov;25(11):1266-71. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on May 10, 2011 11:16

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.