You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
GuanfacinaSpanishINN
GuanfacinumLatinINN
Salts
Name/CAS Structure Properties
Guanfacine Hydrochloride
Thumb
  • InChI Key: DGFYECXYGUIODH-UHFFFAOYSA-N
  • Monoisotopic Mass: 280.988945078
  • Average Mass: 282.554
DBSALT000509
Brand names
NameCompany
EstulicEgis
GuanfacineMylan
IntunivShire
TenexPromius
Brand mixturesNot Available
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassHalobenzenes
Direct parentDichlorobenzenes
Alternative parentsAryl Chlorides; Secondary Carboxylic Acid Amides; Guanidines; Amidines; Enolates; Polyamines; Carboxylic Acids; Organochlorides
Substituentsaryl halide; aryl chloride; guanidine; carboxamide group; secondary carboxylic acid amide; amidine; polyamine; carboxylic acid derivative; enolate; carboxylic acid; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
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
Property Value Probability
Human Intestinal Absorption + 0.9313
Blood Brain Barrier + 0.9567
Caco-2 permeable - 0.5101
P-glycoprotein substrate Non-substrate 0.6778
P-glycoprotein inhibitor I Non-inhibitor 0.8782
P-glycoprotein inhibitor II Non-inhibitor 0.9833
Renal organic cation transporter Non-inhibitor 0.6443
CYP450 2C9 substrate Non-substrate 0.7572
CYP450 2D6 substrate Non-substrate 0.7948
CYP450 3A4 substrate Non-substrate 0.6475
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.8893
CYP450 2D6 substrate Inhibitor 0.8931
CYP450 2C19 substrate Non-inhibitor 0.7376
CYP450 3A4 substrate Non-inhibitor 0.831
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6619
Ames test Non AMES toxic 0.7223
Carcinogenicity Non-carcinogens 0.8107
Biodegradation Not ready biodegradable 0.9843
Rat acute toxicity 2.7408 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9677
hERG inhibition (predictor II) Non-inhibitor 0.9285
Pharmacoeconomics
Manufacturers
  • Shire development inc
  • Amneal pharmaceutical
  • Mikah pharma llc
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
  • Promius pharma llc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Intuniv 1 mg 24 Hour tablet5.72USDtablet
Intuniv 2 mg 24 Hour tablet5.72USDtablet
Intuniv 3 mg 24 Hour tablet5.72USDtablet
Intuniv 4 mg 24 Hour tablet5.72USDtablet
Intuniv er 1 mg tablet5.5USDtablet
Intuniv er 2 mg tablet5.5USDtablet
Intuniv er 3 mg tablet5.5USDtablet
Intuniv er 4 mg tablet5.5USDtablet
Tenex 2 mg tablet4.3USDtablet
Tenex 1 mg tablet2.9USDtablet
Guanfacine HCl 2 mg tablet1.22USDtablet
Guanfacine 2 mg tablet1.18USDtablet
Guanfacine HCl 1 mg tablet0.91USDtablet
Guanfacine 1 mg tablet0.87USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States68117942002-07-042022-07-04
United States58542901995-09-212015-09-21
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 solubility1.39e-01 g/lALOGPS
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 area78.97ChemAxon
rotatable bond count2ChemAxon
refractivity69.63ChemAxon
polarizability21.75ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,632,645.

General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07037
PubChem Compound3519
PubChem Substance46506169
ChemSpider3399
Therapeutic Targets DatabaseDAP000900
PharmGKBPA449825
IUPHAR522
Guide to Pharmacology522
RxListhttp://www.rxlist.com/cgi/generic3/guanfacine.htm
Drugs.comhttp://www.drugs.com/cdi/guanfacine.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/gua1657.shtml
WikipediaGuanfacine
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 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

2. 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

3. 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

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on April 25, 2014 14:55