Banner
targets (1) enzymes (3)
for drugs
Identification
Name Guanfacine
Accession Number DB01018 (APRD00075)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Guanfacina [INN-Spanish]
  • guanfacine
  • Guanfacine HCl
  • Guanfacine Hydrochloride
  • Guanfacinum [INN-Latin]
  • SPD 503
Brand names
  • Estulic
  • Intuniv
  • Tenex
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • Sympatholytics
  • Adrenergic alpha-Agonists
CAS number 29110-47-2
Weight Average: 246.093
Monoisotopic: 245.012267339
Chemical Formula C9H9Cl2N3O
InChI Key InChIKey=INJOMKTZOLKMBF-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)
Plain Text
IUPAC Name
N-carbamimidoyl-2-(2,6-dichlorophenyl)acetamide
SMILES
NC(=N)NC(=O)CC1=C(Cl)C=CC=C1Cl
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenethylamines
Substructures
  • Amino Ketones
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Phenethylamines
  • Guanidines
  • Aromatic compounds
  • Carboxamidines
  • Carboxamides and Derivatives
Pharmacology
Indication For 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.
Pharmacodynamics Guanfacine 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 action Guanfacine 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.
Absorption Rapid and complete, with an oral bioavailability of approximately 80%.
Volume of distribution
  • 6.3 L/kg
Protein binding Approximately 70% bound to plasma proteins, independent of drug concentration.
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 3-hydroxyguanfacine glucuronide
Cytochrome P450 2C9 3-hydroxyguanfacine glucuronide
Cytochrome P450 2C19 3-hydroxyguanfacine glucuronide
Route of elimination In individuals with normal renal function, guanfacine and its metabolites are excreted primarily in the urine.
Half life 17 hours (range 10-30 hours)
Clearance Not Available
Toxicity Symptoms of overdose include drowsiness, lethargy, bradycardia and hypotension. LD50=165mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Shire development inc
  • Amneal pharmaceutical
  • Mikah pharma llc
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
  • Promius pharma llc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Intuniv 1 mg 24 Hour tablet 5.72 USD tablet
Intuniv 2 mg 24 Hour tablet 5.72 USD tablet
Intuniv 3 mg 24 Hour tablet 5.72 USD tablet
Intuniv 4 mg 24 Hour tablet 5.72 USD tablet
Intuniv er 1 mg tablet 5.5 USD tablet
Intuniv er 2 mg tablet 5.5 USD tablet
Intuniv er 3 mg tablet 5.5 USD tablet
Intuniv er 4 mg tablet 5.5 USD tablet
Tenex 2 mg tablet 4.3 USD tablet
Tenex 1 mg tablet 2.9 USD tablet
Guanfacine HCl 2 mg tablet 1.22 USD tablet
Guanfacine 2 mg tablet 1.18 USD tablet
Guanfacine HCl 1 mg tablet 0.91 USD tablet
Guanfacine 1 mg tablet 0.87 USD tablet
Patents
Country Patent Number Approved Expires
United States 6811794 2002-07-04 2022-07-04
United States 5854290 1995-09-21 2015-09-21
Properties
State solid
Melting point 225-227 oC
Experimental Properties
Property Value Source
water solubility 1892 mg/L PhysProp
logP 1.7 PhysProp
Predicted Properties
Property Value Source
water solubility 1.39e-01 g/l ALOGPS
logP 2.28 ALOGPS
logP 1.74 ChemAxon Molconvert
logS -3.25 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 78.97 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 69.63 ChemAxon Molconvert
polarizability 21.74 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07037 Link_out
PubChem Compound 3519 Link_out
PubChem Substance 46506169 Link_out
ChemSpider 3399 Link_out
Therapeutic Targets Database DAP000900 Link_out
PharmGKB PA449825 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic3/guanfacine.htm Link_out
Drugs.com http://www.drugs.com/cdi/guanfacine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/gua1657.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Guanfacine Link_out
ATC Codes
  • C02AC02
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
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. 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
Enzymes

1. Cytochrome P450 3A4

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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Drug created on June 13, 2005 07:24 / Updated on June 07, 2011 21:26

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.