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Identification
NameGuanabenz
Accession NumberDB00629  (APRD00487)
TypeSmall Molecule
GroupsApproved
Description

An alpha-2 selective adrenergic agonist used as an antihypertensive agent. [PubChem]

Structure
Thumb
Synonyms
Guanabenz
Guanabenzo
Guanabenzum
WY-8678
Wytensin
External Identifiers
  • BR 750
  • FLA 137
  • GBZ
  • SD 15468
  • Wy 8678
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LisapresLibbs
RexiteneL.P.B.
WytensAlfresa Pharma
WytensinWyeth
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Guanabenz Acetate
Thumb
  • InChI Key: MCSPBPXATWBACD-GAYQJXMFSA-N
  • Monoisotopic Mass: 290.033731062
  • Average Mass: 291.134
DBSALT000649
Categories
UNIIGGD30112WC
CAS number5051-62-7
WeightAverage: 231.082
Monoisotopic: 230.01260169
Chemical FormulaC8H8Cl2N4
InChI KeyInChIKey=WDZVGELJXXEGPV-YIXHJXPBSA-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)/b13-4+
IUPAC Name
2-{[(2,6-dichlorophenyl)methylidene]amino}guanidine
SMILES
NC(N)=NN=CC1=C(Cl)C=CC=C1Cl
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassHalobenzenes
Direct ParentDichlorobenzenes
Alternative Parents
Substituents
  • 1,3-dichlorobenzene
  • Aryl halide
  • Aryl chloride
  • Guanidine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor management of High blood pressure
PharmacodynamicsGuanabenz, a centrally acting α-2 adrenergic agonist, is indicated for treatment of hypertension.
Mechanism of actionGuanabenz'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.
Related Articles
AbsorptionApproximately 75% absorbed from gastrointestinal tract
Volume of distributionNot Available
Protein binding90%
Metabolism

Hepatic

Route of eliminationNot Available
Half life6 hours.
ClearanceNot Available
ToxicityExcessive contraction of the pupils, irritability, low blood pressure, sleepiness, slow heartbeat, sluggishness
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9921
Blood Brain Barrier+0.8593
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.6838
P-glycoprotein inhibitor INon-inhibitor0.9248
P-glycoprotein inhibitor IINon-inhibitor0.9857
Renal organic cation transporterNon-inhibitor0.6424
CYP450 2C9 substrateNon-substrate0.8798
CYP450 2D6 substrateNon-substrate0.9003
CYP450 3A4 substrateNon-substrate0.7563
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.925
CYP450 2D6 inhibitorInhibitor0.884
CYP450 2C19 inhibitorNon-inhibitor0.9158
CYP450 3A4 inhibitorNon-inhibitor0.9135
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8825
Ames testNon AMES toxic0.618
CarcinogenicityNon-carcinogens0.6862
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.8555 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8927
hERG inhibition (predictor II)Non-inhibitor0.9652
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
  • Wyeth ayerst laboratories
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Guanabenz acetate 8 mg tablet2.13USD tablet
Guanabenz acetate 4 mg tablet1.07USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point225-227British Patent 1,019,120.
logP3.2Not Available
Caco2 permeability-4.5ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0889 mg/mLALOGPS
logP2.25ALOGPS
logP1.71ChemAxon
logS-3.4ALOGPS
pKa (Strongest Basic)6.82ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area76.76 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity58.15 m3·mol-1ChemAxon
Polarizability21.58 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

British Patent 1,019,120.

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (219 KB)
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Thioesterase binding
Specific Function:
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 = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
References
  1. Piletz JE, Sletten K: Nonadrenergic imidazoline binding sites on human platelets. J Pharmacol Exp Ther. 1993 Dec;267(3):1493-502. [PubMed:8263811 ]
  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:7903385 ]
  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:8819507 ]
  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:15265636 ]
  5. van Zwieten PA: Centrally acting antihypertensives: a renaissance of interest. Mechanisms and haemodynamics. J Hypertens Suppl. 1997 Jan;15(1):S3-8. [PubMed:9050980 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Epinephrine binding
Specific Function:
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 clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phent...
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Uhlen S, Wikberg JE: Delineation of rat kidney alpha 2A- and alpha 2B-adrenoceptors with [3H]RX821002 radioligand binding: computer modelling reveals that guanfacine is an alpha 2A-selective compound. Eur J Pharmacol. 1991 Sep 17;202(2):235-43. [PubMed:1666366 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
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 N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
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:19754423 ]
  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:9351903 ]
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Drug created on June 13, 2005 07:24 / Updated on January 15, 2016 17:38