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
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)
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1867 |
7.03 null [pKi] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | TENEX Approved UseTenex (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 Date5.30755191E11 |
|||
Primary | TENEX Approved UseINTUNIV® 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 Date5.30755191E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
12 mg single, oral Overdose |
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 |
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%) Sources: Fatigue (2%) Hypotension (1%) Headache (1%) Dizziness (1%) |
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) Sources: Fatigue (below serious, 3 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypertensive | 1% Disc. AE |
12 mg single, oral Overdose |
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 |
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 16.0 |
no | |||
Page: 15.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 16.0 |
no | |||
Page: 15.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 10.0 |
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 |
||
Page: 18.0 |
weak | |||
Page: 10.0 |
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
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Bradycardia during epidural anesthesia in a patient receiving guanfacine. | 1992 Dec |
|
Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension? | 2001 |
|
Effects of alpha-adrenoceptor agonists in chronic morphine administered DSP4-treated rats: evidence for functional cross-sensitization. | 2001 Oct |
|
Why have drug treatments been so disappointing? | 2003 |
|
Hallucinations associated with initiation of guanfacine. | 2003 Dec |
|
Growth hormone response to guanfacine in boys with attention deficit hyperactivity disorder: a preliminary study. | 2003 Fall |
|
The alpha2-adrenergic agonist guanfacine reduces excitability of human motor cortex through disfacilitation and increase of inhibition. | 2003 Oct |
|
Pharmacotherapy of pervasive developmental disorders in children and adolescents. | 2004 |
|
The anticonvulsant and proconvulsant effects of alpha2-adrenoreceptor agonists are mediated by distinct populations of alpha2A-adrenoreceptors. | 2004 |
|
alpha2a adrenoceptors regulate phosphorylation of microtubule-associated protein-2 in cultured cortical neurons. | 2004 |
|
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: an open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728]. | 2004 Apr 29 |
|
Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure. | 2004 Dec |
|
Guanfacine treatment of clozapine-induced sialorrhea. | 2004 Dec |
|
[Tourette syndrome: an analysis of its comorbidity and specific treatment]. | 2004 Feb |
|
Pharmacological management of attention-deficit hyperactivity disorder. | 2004 Jun |
|
Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder. | 2004 Mar |
|
Loss of glutamatergic pyramidal neurons in frontal and temporal cortex resulting from attenuation of FGFR1 signaling is associated with spontaneous hyperactivity in mice. | 2004 Mar 3 |
|
Subtypes of alpha1- and alpha2-adrenoceptors mediating noradrenergic modulation of spontaneous inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus. | 2004 May |
|
Potential noradrenergic targets for cognitive enhancement in schizophrenia. | 2004 May |
|
Noradrenergic alpha-2 agonists have anxiolytic-like actions on stress-related behavior and mesoprefrontal dopamine biochemistry. | 2004 Nov 19 |
|
Methylphenidate an effective treatment for ADHD? | 2004 Oct |
|
Alpha2 adrenergic agonists for the management of opioid withdrawal. | 2004 Oct 18 |
|
Clonidine and guanfacine-induced antinociception in visceral pain: possible role of alpha 2/I2 binding sites. | 2004 Oct 6 |
|
Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders: a retrospective analysis of 80 cases. | 2004 Summer |
|
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 |
|
Aripiprazole in children and adolescents: clinical experience. | 2005 Jul |
|
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 |
|
Recent pharmacologic updates. | 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 |
|
Effect of noradrenergic system on the anxiolytic-like effect of DOI (5-HT2A/2C agonists) in the four-plate test. | 2006 Jan |
|
Noradrenergic modulation of space exploration in visual neglect. | 2006 Jan |
|
Yohimbine acts as a putative in vivo alpha2A/D-antagonist in the rat prefrontal cortex. | 2006 Jul 24 |
|
Tourette's Syndrome. | 2006 Jun |
|
Syncope in children with Tourette's syndrome treated with guanfacine. | 2006 Mar |
|
Heme coordination states of unfolded ferrous cytochrome C. | 2006 Oct 15 |
|
Relative contribution of intracellular and extracellular Ca2+ to alpha2-adrenoceptor-mediated contractions of ovine pulmonary artery. | 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
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/guanfacine.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2884339
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
Edited
Fri Jun 25 21:59:17 UTC 2021
by
admin
on
Fri Jun 25 21:59:17 UTC 2021
|
Record UNII |
30OMY4G3MK
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
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 | ||
---|---|---|---|---|---|
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | ||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | ||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 |
|
|
|||