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Identification
NameGuanfacine
Accession NumberDB01018  (APRD00075)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A centrally acting antihypertensive agent. The drug lowers both systolic and diastolic blood pressure by activating the central nervous system alpha-2 adrenoreceptors, which results in reduced sympathetic outflow leading to reduced vascular tone. Its adverse reactions include dry mouth, sedation, and constipation. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
EstulicNot AvailableNot Available
GuanfacinaSpanishINN
GuanfacinumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Intunivtablet, extended release1 mgoralShire US Manufacturing Inc.2009-09-02Not AvailableUs
Intunivtablet, extended release2 mgoralShire US Manufacturing Inc.2009-09-02Not AvailableUs
Intunivtablet, extended release3 mgoralShire US Manufacturing Inc.2009-09-02Not AvailableUs
Intunivtablet, extended release4 mgoralShire US Manufacturing Inc.2009-09-02Not AvailableUs
IntunivkitShire US Manufacturing Inc.2009-09-02Not AvailableUs
Intunivtablet, extended release1 mgoralTYA Pharmaceuticals2009-09-02Not AvailableUs
Intunivtablet, extended release2 mgoralTYA Pharmaceuticals2009-09-02Not AvailableUs
Tenextablet1 mgoralPromius Pharma, LLC1986-10-27Not AvailableUs
Tenextablet2 mgoralPromius Pharma, LLC1986-10-27Not AvailableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Guanfacinetablet, extended release1 mgoralActavis Pharma, Inc.2014-12-01Not AvailableUs
Guanfacinetablet, extended release2 mgoralActavis Pharma, Inc.2014-12-01Not AvailableUs
Guanfacinetablet, extended release3 mgoralActavis Pharma, Inc.2014-12-01Not AvailableUs
Guanfacinetablet, extended release4 mgoralActavis Pharma, Inc.2014-12-01Not AvailableUs
Guanfacinetablet1 mgoralMylan Pharmaceuticals Inc.1997-01-28Not AvailableUs
Guanfacinetablet2 mgoralMylan Pharmaceuticals Inc.1997-01-28Not AvailableUs
Guanfacinetablet1 mgoralActavis Pharma, Inc.1995-10-17Not AvailableUs
Guanfacinetablet2 mgoralActavis Pharma, Inc.1995-10-17Not AvailableUs
Guanfacine Hydrochloridetablet1 mgoralMajor Pharmaceuticals1998-11-25Not AvailableUs
Guanfacine Hydrochloridetablet2 mgoralMajor Pharmaceuticals1998-11-25Not AvailableUs
Guanfacine Hydrochloridetablet1 mgoralAv Kare, Inc.1998-11-25Not AvailableUs
Guanfacine Hydrochloridetablet2 mgoralAv Kare, Inc.1998-11-25Not AvailableUs
Guanfacinetablet1 mgoralEpic Pharma, LLC2013-12-02Not AvailableUs
Guanfacinetablet2 mgoralEpic Pharma, LLC2013-12-02Not AvailableUs
Guanfacinetablet2 mgoralPhysicians Total Care, Inc.2003-07-31Not AvailableUs
Guanfacinetablet1 mgoralCardinal Health1995-10-17Not AvailableUs
Guanfacinetablet1 mgoralCardinal Health1997-01-27Not AvailableUs
Guanfacinetablet1 mgoralGolden State Medical Supply, Inc.2014-04-22Not AvailableUs
Guanfacinetablet2 mgoralGolden State Medical Supply, Inc.2014-04-22Not AvailableUs
Guanfacine Hydrochloridetablet1 mgoralTYA Pharmaceuticals1998-11-25Not AvailableUs
Guanfacine Hydrochloridetablet1 mgoralAmneal Pharmaceuticals1998-11-25Not AvailableUs
Guanfacine Hydrochloridetablet2 mgoralAmneal Pharmaceuticals1998-11-25Not AvailableUs
Guanfacine Hydrochloridetablet1 mgoralAmerican Health Packaging2014-05-30Not AvailableUs
Guanfacinetablet1 mgoralCarilion Materials Management1995-10-17Not AvailableUs
Over the Counter ProductsNot Available
International Brands
NameCompany
EstulicEgis
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Guanfacine Hydrochloride
Thumb
  • InChI Key: DGFYECXYGUIODH-UHFFFAOYSA-N
  • Monoisotopic Mass: 280.988945078
  • Average Mass: 282.554
DBSALT000509
Categories
CAS number29110-47-2
WeightAverage: 246.093
Monoisotopic: 245.012267339
Chemical FormulaC9H9Cl2N3O
InChI KeyINJOMKTZOLKMBF-UHFFFAOYSA-N
InChI
InChI=1S/C9H9Cl2N3O/c10-6-2-1-3-7(11)5(6)4-8(15)14-9(12)13/h1-3H,4H2,(H4,12,13,14,15)
IUPAC Name
N-carbamimidoyl-2-(2,6-dichlorophenyl)acetamide
SMILES
NC(=N)NC(=O)CC1=C(Cl)C=CC=C1Cl
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylacetamides. These are amide derivatives of phenylacetic acids.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylacetamides
Direct ParentPhenylacetamides
Alternative Parents
Substituents
  • Phenylacetamide
  • 1,3-dichlorobenzene
  • Halobenzene
  • Chlorobenzene
  • Aryl halide
  • Aryl chloride
  • Guanidine
  • Carboxamide group
  • Carboximidamide
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Imine
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor use alone or in combination with other classes of antihypertensive agents in the management of hypertension. Has also been used for the treatment of attention deficit hyperactivity disorder (ADHD) in pediatric patients.
PharmacodynamicsGuanfacine is a phenylacetyl-guanidine derivative hypotensive and a centrally-acting, alpha(2)-adrenergic receptor agonist used alone or in combination with other drugs for the treatment of hypertension.
Mechanism of actionGuanfacine selectively stimulates central alpha(2)-adrenergic receptors, resulting in inhibition of sympathetic vasomotor centers, which contributes predominantly to the hypotensive effects of the drug. Central effects of guanfacine lead to reduced peripheral sympathetic nerve impulses from the vasomotor center to the heart and blood vessels. This results in a decrease in peripheral vascular resistance and a reduction in heart rate. The stimulation of peripheral alpha(2)-adrenergic receptors may also contribute to hypotensive effects.
AbsorptionRapid and complete, with an oral bioavailability of approximately 80%.
Volume of distribution
  • 6.3 L/kg
Protein bindingApproximately 70% bound to plasma proteins, independent of drug concentration.
Metabolism

Hepatic

SubstrateEnzymesProduct
Guanfacine
3-hydroxyguanfacine glucuronideDetails
Route of eliminationIn individuals with normal renal function, guanfacine and its metabolites are excreted primarily in the urine.
Half life17 hours (range 10-30 hours)
ClearanceNot Available
ToxicitySymptoms of overdose include drowsiness, lethargy, bradycardia and hypotension. LD50=165mg/kg (orally in mice)
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+0.9313
Blood Brain Barrier+0.9567
Caco-2 permeable-0.5101
P-glycoprotein substrateNon-substrate0.6778
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.9833
Renal organic cation transporterNon-inhibitor0.6443
CYP450 2C9 substrateNon-substrate0.7572
CYP450 2D6 substrateNon-substrate0.7948
CYP450 3A4 substrateNon-substrate0.6475
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 substrateNon-inhibitor0.8893
CYP450 2D6 substrateInhibitor0.8931
CYP450 2C19 substrateNon-inhibitor0.7376
CYP450 3A4 substrateNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6619
Ames testNon AMES toxic0.7223
CarcinogenicityNon-carcinogens0.8107
BiodegradationNot ready biodegradable0.9843
Rat acute toxicity2.7408 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9677
hERG inhibition (predictor II)Non-inhibitor0.9285
Pharmacoeconomics
Manufacturers
  • Shire development inc
  • Amneal pharmaceutical
  • Mikah pharma llc
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
  • Promius pharma llc
Packagers
Dosage forms
FormRouteStrength
Kit
Tabletoral1 mg
Tabletoral2 mg
Tablet, extended releaseoral1 mg
Tablet, extended releaseoral2 mg
Tablet, extended releaseoral3 mg
Tablet, extended releaseoral4 mg
Prices
Unit descriptionCostUnit
Intuniv 1 mg 24 Hour tablet5.72USD tablet
Intuniv 2 mg 24 Hour tablet5.72USD tablet
Intuniv 3 mg 24 Hour tablet5.72USD tablet
Intuniv 4 mg 24 Hour tablet5.72USD tablet
Intuniv er 1 mg tablet5.5USD tablet
Intuniv er 2 mg tablet5.5USD tablet
Intuniv er 3 mg tablet5.5USD tablet
Intuniv er 4 mg tablet5.5USD tablet
Tenex 2 mg tablet4.3USD tablet
Tenex 1 mg tablet2.9USD tablet
Guanfacine HCl 2 mg tablet1.22USD tablet
Guanfacine 2 mg tablet1.18USD tablet
Guanfacine HCl 1 mg tablet0.91USD tablet
Guanfacine 1 mg tablet0.87USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States58542901995-09-212015-09-21
United States68117942002-07-042022-07-04
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point213-216U.S. Patent 3,632,645.
water solubility1892 mg/LNot Available
logP1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.139 mg/mLALOGPS
logP2.28ALOGPS
logP1.74ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)12.94ChemAxon
pKa (Strongest Basic)6.65ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area78.97 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity69.63 m3·mol-1ChemAxon
Polarizability21.75 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

U.S. Patent 3,632,645.

General ReferenceNot Available
External Links
ATC CodesC02AC02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
EtravirineGuanfacine, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to increase guanfacine dosage up to 8mg/day, as tolerated, and to monitor gefitinib therapy.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TrimipramineTrimipramine may reduce the antihypertensive effect of the alpha2-agonist, Guanfacine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Guanfacine should be withdrawn very gradually to reduce the risk of hypertensive crisis.
Food InteractionsNot Available

Targets

1. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

References:

  1. Avery RA, Franowicz JS, Studholme C, van Dyck CH, Arnsten AF: The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task. Neuropsychopharmacology. 2000 Sep;23(3):240-9. Pubmed
  2. Sagvolden T: The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD). Behav Brain Funct. 2006 Dec 15;2:41. Pubmed
  3. Yuan R, Wu Z, Kostenyuk IA, Burns JK: G-protein-coupled alpha2A-adrenoreceptor agonists differentially alter citrus leaf and fruit abscission by affecting expression of ACC synthase and ACC oxidase. J Exp Bot. 2005 Jul;56(417):1867-75. Epub 2005 May 31. Pubmed
  4. Birnbaum SG, Podell DM, Arnsten AF: Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats. Pharmacol Biochem Behav. 2000 Nov;67(3):397-403. Pubmed
  5. Millan MJ: Evidence that an alpha 2A-adrenoceptor subtype mediates antinociception in mice. Eur J Pharmacol. 1992 May 14;215(2-3):355-6. Pubmed
  6. Stahl SM: Mechanism of action of alpha 2A-adrenergic agonists in attention-deficit/hyperactivity disorder with or without oppositional symptoms. J Clin Psychiatry. 2010 Mar;71(3):223-4. Pubmed

2. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

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

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Clement B, Demesmaeker M: Microsomal catalyzed N-hydroxylation of guanfacine and reduction of N-hydroxyguanfacine. Arch Pharm (Weinheim). 1997 Oct;330(9-10):303-6. Pubmed
  2. Guillouzo A, Le Bigot JF, Guguen-Guillouzo C, Kiechel JR: Presence of phase I and phase II drug metabolizing enzymes in cultured human foetal hepatocytes. Biochem Pharmacol. 1982 Jul 15;31(14):2427-30. Pubmed

2. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Clement B, Demesmaeker M: Microsomal catalyzed N-hydroxylation of guanfacine and reduction of N-hydroxyguanfacine. Arch Pharm (Weinheim). 1997 Oct;330(9-10):303-6. Pubmed
  2. Guillouzo A, Le Bigot JF, Guguen-Guillouzo C, Kiechel JR: Presence of phase I and phase II drug metabolizing enzymes in cultured human foetal hepatocytes. Biochem Pharmacol. 1982 Jul 15;31(14):2427-30. Pubmed

3. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Clement B, Demesmaeker M: Microsomal catalyzed N-hydroxylation of guanfacine and reduction of N-hydroxyguanfacine. Arch Pharm (Weinheim). 1997 Oct;330(9-10):303-6. Pubmed
  2. Guillouzo A, Le Bigot JF, Guguen-Guillouzo C, Kiechel JR: Presence of phase I and phase II drug metabolizing enzymes in cultured human foetal hepatocytes. Biochem Pharmacol. 1982 Jul 15;31(14):2427-30. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 25, 2014 14:55