Identification

Name
Guanabenz
Accession Number
DB00629  (APRD00487)
Type
Small Molecule
Groups
Approved, Investigational
Description

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

Structure
Thumb
Synonyms
  • Guanabenz
  • Guanabenzo
  • Guanabenzum
External IDs
BR 750 / FLA 137 / GBZ / NSC-68982 / SD 15468 / Wy 8678 / WY-8678
Product Ingredients
IngredientUNIICASInChI Key
Guanabenz Acetate443O19GK1A23256-50-0MCSPBPXATWBACD-GAYQJXMFSA-N
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Guanabenz AcetateTablet4 mg/1OralIVAX Pharmaceuticals, Inc.1995-04-072012-08-31Us
Guanabenz AcetateTablet8 mg/1OralIVAX Pharmaceuticals, Inc.1995-04-072012-10-31Us
International/Other Brands
Lisapres (Libbs) / Rexitene (L.P.B.) / Wytens (Alfresa Pharma) / Wytensin (Wyeth)
Categories
UNII
GGD30112WC
CAS number
5051-62-7
Weight
Average: 231.082
Monoisotopic: 230.01260169
Chemical Formula
C8H8Cl2N4
InChI Key
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

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.

TargetActionsOrganism
AAlpha-2A adrenergic receptor
agonist
Human
UAlpha-2B adrenergic receptor
binder
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Guanabenz.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidGuanabenz may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Guanabenz is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of hypertension can be increased when Guanabenz is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of hypertension can be increased when Guanabenz is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Guanabenz.
3,4-MethylenedioxyamphetamineThe risk or severity of hypertension can be increased when Guanabenz is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of hypertension can be increased when Guanabenz is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of hypertension can be increased when Guanabenz is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of hypertension can be increased when Guanabenz is combined with 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
Not Available

References

Synthesis Reference

British Patent 1,019,120.

General References
Not Available
External Links
KEGG Drug
D04375
KEGG Compound
C07034
PubChem Compound
3517
PubChem Substance
46505200
ChemSpider
4642445
ChEBI
5553
ChEMBL
CHEMBL420
Therapeutic Targets Database
DAP000232
PharmGKB
PA164774903
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Guanabenz
FDA label
Download (219 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedTreatmentDisseminated Sclerosis / Relapsing Remitting Multiple Sclerosis (RRMS)1
Not AvailableTerminatedTreatmentBone Cancer / Metastasis1

Pharmacoeconomics

Manufacturers
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
  • Wyeth ayerst laboratories
Packagers
  • Ivax Pharmaceuticals
  • Letco Medical Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Pharmaceutical Utilization Management Program VA Inc.
Dosage forms
FormRouteStrength
TabletOral4 mg/1
TabletOral8 mg/1
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)225-227British 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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-2900000000-beb608df56c6a048bf6a

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Dichlorobenzenes
Alternative Parents
Aryl chlorides / Guanidines / Carboximidamides / Organopnictogen compounds / Organochlorides / Imines / Hydrocarbon derivatives
Substituents
1,3-dichlorobenzene / Aryl halide / Aryl chloride / Guanidine / Carboximidamide / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Organochloride
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not 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 oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
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...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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]
  3. CYP1A2 cancer.gov document [File]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:40