U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C9H9Cl2N3O
Molecular Weight 246.0935
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GUANFACINE

SMILES

c1cc(c(CC(=NC(=N)N)O)c(c1)Cl)Cl

InChI

InChIKey=INJOMKTZOLKMBF-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C9H9Cl2N3O
Molecular Weight 246.0935
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Guanfacine (marketed under the brand names Estulic, Tenex and the extended release Intuniv) is a sympatholytic drug, indicated for the management of hypertension. Tenex (guanfacine hydrochloride) is an orally active antihypertensive agent whose principal mechanism of action appears to be stimulation of central α2-adrenergic receptors. By stimulating these receptors, guanfacine reduces 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. Guanfacine is also used in the treatment of attention deficit hyperactivity disorder. Intuniv is an extended-release version of guanfacine that is used to treat symptoms of ADHD. It can be used by itself or with stimulant medications also used to treat symptoms of ADHD.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TENEX

Approved Use

Tenex (guanfacine hydrochloride) is indicated in the management of hypertension. Tenex may be given alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Launch Date

5.30755191E11
Primary
TENEX

Approved Use

INTUNIV® is a central alpha2A-adrenergic receptor agonist indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications

Launch Date

5.30755191E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7 ng/mL
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GUANFACINE plasma
Homo sapiens
population: UNKNOWN
age: ADOLESCENT
sex: UNKNOWN
food status: UNKNOWN
10 ng/mL
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GUANFACINE plasma
Homo sapiens
population: UNKNOWN
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
2.5 ng/mL
1 mg 1 times / day multiple, oral
dose: 1 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GUANFACINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
116 ng × h/mL
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GUANFACINE plasma
Homo sapiens
population: UNKNOWN
age: ADOLESCENT
sex: UNKNOWN
food status: UNKNOWN
162 ng × h/mL
4 mg 1 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GUANFACINE plasma
Homo sapiens
population: UNKNOWN
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
56 ng × h/mL
1 mg 1 times / day multiple, oral
dose: 1 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GUANFACINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
16 h
1 mg 1 times / day multiple, oral
dose: 1 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GUANFACINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
30%
1 mg 1 times / day multiple, oral
dose: 1 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GUANFACINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
12 mg single, oral
Overdose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources:
unhealthy, 12 years
n = 1
Health Status: unhealthy
Condition: ADHD and Tourette syndrome
Age Group: 12 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Hypertensive...
AEs leading to
discontinuation/dose reduction:
Hypertensive (1%)
Sources:
80 mg single, oral
Overdose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
unhealthy, 17 years
n = 1
Health Status: unhealthy
Condition: ADHD
Age Group: 17 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Cardiogenic pulmonary edema...
AEs leading to
discontinuation/dose reduction:
Cardiogenic pulmonary edema (1%)
Sources:
4 mg 1 times / day steady, oral
Recommended
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children and adolescents
n = 513
Health Status: unhealthy
Condition: ADHD
Age Group: children and adolescents
Sex: M+F
Population Size: 513
Sources:
Disc. AE: Somnolence, Fatigue...
AEs leading to
discontinuation/dose reduction:
Somnolence (6%)
Fatigue (2%)
Hypotension (1%)
Headache (1%)
Dizziness (1%)
Sources:
4 mg 1 times / day steady, oral
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children
n = 16
Health Status: unhealthy
Condition: Attention Deficit Hyperactivity Disorder
Age Group: children
Population Size: 16
Sources:
Other AEs: Sedation, Fatigue...
Other AEs:
Sedation (below serious, 5 patients)
Fatigue (below serious, 3 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypertensive 1%
Disc. AE
12 mg single, oral
Overdose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources:
unhealthy, 12 years
n = 1
Health Status: unhealthy
Condition: ADHD and Tourette syndrome
Age Group: 12 years
Sex: M
Population Size: 1
Sources:
Cardiogenic pulmonary edema 1%
Disc. AE
80 mg single, oral
Overdose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
unhealthy, 17 years
n = 1
Health Status: unhealthy
Condition: ADHD
Age Group: 17 years
Sex: M
Population Size: 1
Sources:
Dizziness 1%
Disc. AE
4 mg 1 times / day steady, oral
Recommended
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children and adolescents
n = 513
Health Status: unhealthy
Condition: ADHD
Age Group: children and adolescents
Sex: M+F
Population Size: 513
Sources:
Headache 1%
Disc. AE
4 mg 1 times / day steady, oral
Recommended
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children and adolescents
n = 513
Health Status: unhealthy
Condition: ADHD
Age Group: children and adolescents
Sex: M+F
Population Size: 513
Sources:
Hypotension 1%
Disc. AE
4 mg 1 times / day steady, oral
Recommended
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children and adolescents
n = 513
Health Status: unhealthy
Condition: ADHD
Age Group: children and adolescents
Sex: M+F
Population Size: 513
Sources:
Fatigue 2%
Disc. AE
4 mg 1 times / day steady, oral
Recommended
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children and adolescents
n = 513
Health Status: unhealthy
Condition: ADHD
Age Group: children and adolescents
Sex: M+F
Population Size: 513
Sources:
Somnolence 6%
Disc. AE
4 mg 1 times / day steady, oral
Recommended
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children and adolescents
n = 513
Health Status: unhealthy
Condition: ADHD
Age Group: children and adolescents
Sex: M+F
Population Size: 513
Sources:
Fatigue below serious, 3 patients
4 mg 1 times / day steady, oral
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children
n = 16
Health Status: unhealthy
Condition: Attention Deficit Hyperactivity Disorder
Age Group: children
Population Size: 16
Sources:
Sedation below serious, 5 patients
4 mg 1 times / day steady, oral
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
unhealthy, children
n = 16
Health Status: unhealthy
Condition: Attention Deficit Hyperactivity Disorder
Age Group: children
Population Size: 16
Sources:
Overview

Overview

Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: There was a significant decrease in the rate and extent of guanfacine exposure when co-administered with rifampin, a CYP3A4 inducer. The exposure to guanfacine decreased by 70% (AUC)
Page: 10.0
weak
yes
yes (co-administration study)
Comment: There was a substantial increase in the rate and extent of guanfacine exposure when administered with ketoconazole; the guanfacine exposure increased 3-fold (AUC)
Page: 10.0
Tox targets

Tox targets

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension?
2001
Effects of rilmenidine and guanfacine in acute renal denervated rats.
2002
Alpha 2-adrenoceptor stimulation in the periventricular nucleus increases urine flow rate with minimal effects on blood pressure.
2002
Role of alpha 2-adrenoceptors and imidazoline receptors in the A5 region in the regulation of renal function in the rat.
2002
Attention deficit disorder in adults.
2002 Jun
Seizures and extrapyramidal symptoms in a patient with Tourette's syndrome, Asperger's syndrome, and multiple sclerosis treated with interferon beta-1a and clomipramine.
2002 Nov
Where do we go from here? The importance of initial values.
2002 Nov
Epidemiology and toxicity of pediatric guanfacine exposures.
2002 Nov
Neuropsychiatric effects of guanfacine in children with mild tourette syndrome: a pilot study.
2002 Nov-Dec
Psychopharmacology of ADHD in adolescents.
2002 Oct
Alpha2 adrenergic agonists for the management of opioid withdrawal.
2003
Non-stimulant treatment of attention-deficit/hyperactivity disorder.
2003 Apr
Stimulation of interleukin-12 production in mouse macrophages via activation of p38 mitogen-activated protein kinase by alpha2-adrenoceptor agonists.
2003 Apr 25
Hallucinations associated with initiation of guanfacine.
2003 Dec
An antihypokinesic action of alpha2-adrenoceptors upon MPTP-induced behaviour deficits in mice.
2003 Feb
Frontotemporal dementias: clinical features and management.
2003 Jan
Evaluation of the genes for the adrenergic receptors alpha 2A and alpha 1C and Gilles de la Tourette Syndrome.
2003 May 15
Epinephrine reduces the nerve conduction blockage induced by high-potassium in mammalian sciatic nerve.
2003 Sep 5
Pharmacotherapy of pervasive developmental disorders in children and adolescents.
2004
alpha2a adrenoceptors regulate phosphorylation of microtubule-associated protein-2 in cultured cortical neurons.
2004
Guanfacine treatment of clozapine-induced sialorrhea.
2004 Dec
New options in the pharmacological management of attention-deficit/hyperactivity disorder.
2004 Jul
Pharmacological management of attention-deficit hyperactivity disorder.
2004 Jun
[Centrally-acting antihypertensive drugs].
2004 Mar
Subtypes of alpha1- and alpha2-adrenoceptors mediating noradrenergic modulation of spontaneous inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus.
2004 May
Noradrenergic alpha-2 agonists have anxiolytic-like actions on stress-related behavior and mesoprefrontal dopamine biochemistry.
2004 Nov 19
Mania induction associated with atomoxetine.
2004 Oct
Alpha2 adrenergic agonists for the management of opioid withdrawal.
2004 Oct 18
Enhanced visuomotor associative learning following stimulation of alpha 2A-adrenoceptors in the ventral prefrontal cortex in monkeys.
2004 Oct 22
Clonidine and guanfacine-induced antinociception in visceral pain: possible role of alpha 2/I2 binding sites.
2004 Oct 6
Nonstimulant therapies for attention-deficit hyperactivity disorder (ADHD) in children and adults.
2005
Alpha-2 adrenoceptor activation inhibits phencyclidine-induced deficits of spatial working memory in rats.
2005 Aug
Impaired visuospatial divided attention in the spontaneously hypertensive rat.
2005 Feb 28
Locomotor hyperactivity induced by blockade of prefrontal cortical alpha2-adrenoceptors in monkeys.
2005 Jan 15
G-protein-coupled alpha2A-adrenoreceptor agonists differentially alter citrus leaf and fruit abscission by affecting expression of ACC synthase and ACC oxidase.
2005 Jul
Yohimbine disrupts prepulse inhibition in rats via action at 5-HT1A receptors, not alpha2-adrenoceptors.
2005 Jul
Animal models of attention-deficit hyperactivity disorder.
2005 Jul 15
Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions.
2005 Jun 1
The safety of non-stimulant agents for the treatment of attention-deficit hyperactivity disorder.
2005 Mar
An open-label, prospective study of guanfacine in children with ADHD and tic disorders.
2005 Nov
Lack of effects of guanfacine on executive and memory functions in healthy male volunteers.
2005 Oct
Central sympathetic inhibition augments sleep-related ultradian rhythm of parasympathetic tone in patients with chronic heart failure.
2005 Sep
Mechanism of action of agents used in attention-deficit/hyperactivity disorder.
2006
Introduction: new developments in the treatment of attention-deficit/hyperactivity disorder.
2006
Guanfacine produces differential effects in frontal cortex compared with striatum: assessed by phMRI BOLD contrast.
2006 Dec
New developments in the treatment of ADHD.
2006 Jan
Heme coordination states of unfolded ferrous cytochrome C.
2006 Oct 15
Discriminative stimulus properties of the selective and highly potent alpha2-adrenoceptor agonist, S18616, in rats: mediation by the alpha2A subtype, and blockade by the atypical antidepressants, mirtazapine and mianserin.
2006 Sep
Differential noradrenergic influence on seizure expression in genetically Fast and Slow kindling rat strains during massed trial stimulation of the amygdala.
2007 Feb
The effects of guanfacine on context processing abnormalities in schizotypal personality disorder.
2007 May 15
Patents

Sample Use Guides

Usual Adult Dose for Hypertension Initial dose: 1 mg orally once a day at bedtime; may increase to 2 mg once a day if satisfactory result not achieved after 3 to 4 weeks. Usual Pediatric Dose for Attention Deficit Disorder 6 YEARS TO LESS THAN 18 YEARS: Initial dose: 1 mg orally once a day, either in the morning or evening, at approximately the same time each day; may adjust in increments of no more than 1 mg/week. Recommended target dose: 0.05 to 0.12 mg/kg/day (total daily dose between 1 and 7 mg) once a day, depending on clinical response and tolerability Maximum dose: 6 to 12 years: Doses above 4 mg/day have not been evaluated; 13 to 17 years: Doses above 7 mg/day have not been evaluated.
Route of Administration: Oral
In Vitro Use Guide
Guanfacine and clonidine at relatively high concentrations (10(-6)-10(-4) M) produced contractions of the rat vas deferens which were antagonized by prazosin.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:59:17 UTC 2021
Edited
by admin
on Fri Jun 25 21:59:17 UTC 2021
Record UNII
30OMY4G3MK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GUANFACINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
N-AMIDINO-2-(2,6-DICHLOROPHENYL)ACETAMIDE
Systematic Name English
GUANFACINE [MI]
Common Name English
GUANFACINE [VANDF]
Common Name English
ESTULIC
Brand Name English
GUANFACINE [INN]
Common Name English
NSC-759121
Code English
BENZENEACETAMIDE, N-(AMINOIMINOMETHYL)-2,6-DICHLORO-
Systematic Name English
GUANFACINE [WHO-DD]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175554
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
FDA ORPHAN DRUG 124199
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
NDF-RT N0000009918
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
WHO-ATC C02AC02
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
NCI_THESAURUS C270
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
FDA ORPHAN DRUG 405313
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
WHO-VATC QC02AC02
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
LIVERTOX 474
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
Code System Code Type Description
LACTMED
Guanfacine
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
FDA UNII
30OMY4G3MK
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
IUPHAR
522
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
ChEMBL
CHEMBL862
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
EPA CompTox
29110-47-2
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
DRUG BANK
DB01018
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
RXCUI
40114
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY RxNorm
CAS
29110-47-2
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
MESH
D016316
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
DRUG CENTRAL
1343
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
MERCK INDEX
M5866
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY Merck Index
INN
3999
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
ECHA (EC/EINECS)
249-442-8
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
EVMPD
SUB07985MIG
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
PUBCHEM
3519
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
NCI_THESAURUS
C61779
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
WIKIPEDIA
GUANFACINE
Created by admin on Fri Jun 25 21:59:17 UTC 2021 , Edited by admin on Fri Jun 25 21:59:17 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> AGONIST
SHORT-ACTING
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC