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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2019-01-11 19:35:08 UTC
HMDB IDHMDB0015153
Secondary Accession Numbers
  • HMDB15153
Metabolite Identification
Common NameGuanfacine
DescriptionA 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
Data?1547235308
Synonyms
ValueSource
EstulicKegg
SPD 503HMDB
Monohydrochloride, guanfacineMeSH
Guanfacine monohydrochlorideMeSH
TenexMeSH
Hydrochloride, guanfacineMeSH
Guanfacine hydrochlorideMeSH
Chemical FormulaC9H9Cl2N3O
Average Molecular Weight246.093
Monoisotopic Molecular Weight245.012267339
IUPAC NameN-carbamimidoyl-2-(2,6-dichlorophenyl)acetamide
Traditional Nameguanfacine
CAS Registry Number29110-47-2
SMILES
NC(=N)NC(=O)CC1=C(Cl)C=CC=C1Cl
InChI Identifier
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)
InChI KeyINJOMKTZOLKMBF-UHFFFAOYSA-N
Chemical 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 chloride
  • Aryl halide
  • Carboximidamide
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Imine
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point225 - 227 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.14 g/LNot Available
LogP1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.14 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 Area78.97 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity69.63 m³·mol⁻¹ChemAxon
Polarizability21.75 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4l-5900000000-766dd9f92ab525fb3d7fJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-2190000000-f396a1e8e135a8e36357JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-06ri-2940000000-5a7460d90b0e4e64ca27JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-5900000000-722b0c3c89afd7b7ebabJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-3190000000-3e0c32003f6e9cdb1622JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0zfu-8590000000-95737b8dd85b7d5f0970JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-e0d6699b8eaef7231c16JSpectraViewer | MoNA
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01018 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01018 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01018
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3399
KEGG Compound IDC07037
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkGuanfacine
METLIN IDNot Available
PubChem Compound3519
PDB IDNot Available
ChEBI ID166029
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
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 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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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:9396389 ]
  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:6751332 ]
General function:
Involved in monooxygenase activity
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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
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:9396389 ]
  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:6751332 ]
General function:
Involved in monooxygenase activity
Specific function:
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.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
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:9396389 ]
  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:6751332 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular weight:
48956.3
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:10942848 ]
  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:17173664 ]
  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:15928018 ]
  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:11164065 ]
  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:1356794 ]
  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. doi: 10.4088/JCP.09bs05899pur. [PubMed:20331927 ]