Details
Stereochemistry | ACHIRAL |
Molecular Formula | C9H9Cl2N3O |
Molecular Weight | 246.093 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=N)NC(=O)CC1=C(Cl)C=CC=C1Cl
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 | 246.093 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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 Date1986 |
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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 Date1986 |
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 |
---|---|---|
Alpha2 adrenergic agonists for the management of opioid withdrawal. | 2001 |
|
Alpha 2-adrenoceptor stimulation in the periventricular nucleus increases urine flow rate with minimal effects on blood pressure. | 2002 |
|
Testosterone dependence of salt-induced hypertension in Sabra rats and role of renal alpha(2)-adrenoceptor subtypes. | 2002 Jan |
|
Assessing the molecular genetics of attention networks. | 2002 Oct 4 |
|
Non-stimulant treatment of attention-deficit/hyperactivity disorder. | 2003 Apr |
|
Novel hypotensive agents from Verbesina caracasana: structure, synthesis and pharmacology. | 2003 Sep |
|
Epinephrine reduces the nerve conduction blockage induced by high-potassium in mammalian sciatic nerve. | 2003 Sep 5 |
|
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 |
|
New options in the pharmacological management of attention-deficit/hyperactivity disorder. | 2004 Jul |
|
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 |
|
Mania induction associated with atomoxetine. | 2004 Oct |
|
Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders: a retrospective analysis of 80 cases. | 2004 Summer |
|
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 |
|
An open-label, prospective study of guanfacine in children with ADHD and tic disorders. | 2005 Nov |
|
Recent pharmacologic updates. | 2005 Oct |
|
Lack of effects of guanfacine on executive and memory functions in healthy male volunteers. | 2005 Oct |
|
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 |
|
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 |
|
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 Dec 15 15:12:35 GMT 2023
by
admin
on
Fri Dec 15 15:12:35 GMT 2023
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Record UNII |
30OMY4G3MK
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000175554
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FDA ORPHAN DRUG |
124199
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NDF-RT |
N0000009918
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WHO-ATC |
C02AC02
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NCI_THESAURUS |
C270
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FDA ORPHAN DRUG |
405313
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WHO-VATC |
QC02AC02
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LIVERTOX |
NBK548586
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Guanfacine
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30OMY4G3MK
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30OMY4G3MK
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522
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CHEMBL862
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759121
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DTXSID9046944
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DB01018
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40114
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29110-47-2
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D016316
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1343
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m5866
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3999
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249-442-8
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100000084474
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SUB07985MIG
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3519
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C61779
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GUANFACINE
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT | |||
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TARGET -> AGONIST |
SHORT-ACTING
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
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PRODRUG -> METABOLITE ACTIVE |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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