GUANFACINE

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

Structure Search

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)

HIDE SMILES / InChI

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019032s021lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdfhttps://www.medkoo.com/products/7825

Etiguanfacine, also known as SSP-1871, is an α2-adrenoreceptor agonist.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-2a adrenergic receptor 61 Target ID: CHEMBL1867 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019032s021lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9605427	Agonist 2662		7.03 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 549 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019032s021lbl.pdf	Primary		Approved 8360	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
Attention deficit hyperactivity disorder 68 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	Primary		Approved 8360	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

C_max

Value	Dose	Analyte	Population
7 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	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	Analyte	Population
116 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
16 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
30% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	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 Dose: 12 mg Route: oral Route: single Dose: 12 mg Sources: https://pubmed.ncbi.nlm.nih.gov/23925253/	unhealthy, 12 years n = 1 Health Status: unhealthy Condition: ADHD and Tourette syndrome Age Group: 12 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/23925253/	Disc. AE: Hypertensive... AEs leading to discontinuation/dose reduction: Hypertensive (1%) Sources: https://pubmed.ncbi.nlm.nih.gov/23925253/
80 mg single, oral Overdose Dose: 80 mg Route: oral Route: single Dose: 80 mg Sources: https://pubmed.ncbi.nlm.nih.gov/33069545/	unhealthy, 17 years n = 1 Health Status: unhealthy Condition: ADHD Age Group: 17 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/33069545/	Disc. AE: Cardiogenic pulmonary edema... AEs leading to discontinuation/dose reduction: Cardiogenic pulmonary edema (1%) Sources: https://pubmed.ncbi.nlm.nih.gov/33069545/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	unhealthy, children and adolescents n = 513 Health Status: unhealthy Condition: ADHD Age Group: children and adolescents Sex: M+F Population Size: 513 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	Disc. AE: Somnolence, Fatigue... AEs leading to discontinuation/dose reduction: Somnolence (6%) Fatigue (2%) Hypotension (1%) Headache (1%) Dizziness (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf
4 mg 1 times / day steady, oral Dose: 4 mg, 1 times / day Route: oral Route: steady Dose: 4 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01069523	unhealthy, children n = 16 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Age Group: children Population Size: 16 Sources: https://clinicaltrials.gov/ct2/show/NCT01069523	Other AEs: Sedation, Fatigue... Other AEs: Sedation (below serious, 5 patients) Fatigue (below serious, 3 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01069523

AEs

AE	Significance	Dose	Population
Hypertensive	1% Disc. AE	12 mg single, oral Overdose Dose: 12 mg Route: oral Route: single Dose: 12 mg Sources: https://pubmed.ncbi.nlm.nih.gov/23925253/	unhealthy, 12 years n = 1 Health Status: unhealthy Condition: ADHD and Tourette syndrome Age Group: 12 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/23925253/
Cardiogenic pulmonary edema	1% Disc. AE	80 mg single, oral Overdose Dose: 80 mg Route: oral Route: single Dose: 80 mg Sources: https://pubmed.ncbi.nlm.nih.gov/33069545/	unhealthy, 17 years n = 1 Health Status: unhealthy Condition: ADHD Age Group: 17 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/33069545/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	unhealthy, children and adolescents n = 513 Health Status: unhealthy Condition: ADHD Age Group: children and adolescents Sex: M+F Population Size: 513 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	unhealthy, children and adolescents n = 513 Health Status: unhealthy Condition: ADHD Age Group: children and adolescents Sex: M+F Population Size: 513 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	unhealthy, children and adolescents n = 513 Health Status: unhealthy Condition: ADHD Age Group: children and adolescents Sex: M+F Population Size: 513 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	unhealthy, children and adolescents n = 513 Health Status: unhealthy Condition: ADHD Age Group: children and adolescents Sex: M+F Population Size: 513 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf	unhealthy, children and adolescents n = 513 Health Status: unhealthy Condition: ADHD Age Group: children and adolescents Sex: M+F Population Size: 513 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf
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: https://clinicaltrials.gov/ct2/show/NCT01069523	unhealthy, children n = 16 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Age Group: children Population Size: 16 Sources: https://clinicaltrials.gov/ct2/show/NCT01069523
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: https://clinicaltrials.gov/ct2/show/NCT01069523	unhealthy, children n = 16 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Age Group: children Population Size: 16 Sources: https://clinicaltrials.gov/ct2/show/NCT01069523

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	inhibitor 1752	inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2C8 901 CYP2C19 1463 CYP3A4/5 273 CYP2B6 799	CYP3A4/5 85 P-gp 1527	CYP3A 126 CYP1A2 689 CYP2B6 538

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022037s018lbl.pdf#page=16 Page: 16.0	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=15 Page: 15.0	no
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022037s018lbl.pdf#page=16 Page: 16.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022037s018lbl.pdf#page=16 Page: 16.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=15 Page: 15.0	no
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=15 Page: 15.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=15 Page: 15.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=15 Page: 15.0	no
CYP3A 295	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022037s018lbl.pdf#page=16 Page: 16.0	no
CYP3A4/5 330	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=15 Page: 15.0	no

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=10 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) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=10 Page: 10.0
P-gp 1527	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173033/ Page: 18.0	weak
CYP3A4/5 85	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=10 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) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf#page=10 Page: 10.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://www.tga.gov.au/sites/default/files/auspar-guanfacine-180503.pdf#page=30

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY546722	https://www.001chemical.com/chem/29110-47-2
AHH Chemical co.,ltd	MR-1013815	http://www.ahhchemical.com/product/MR-1013815.html
Alsachim	928	http://www.alsachim.com/product-C1246-glo.bal-view.html
Ambinter	Amb10843802	http://www.ambinter.com/reference/10843802
Angel Pharmatech	AG302778	http://www.angelpharmatech.com/29110-47-2.html
Angene	AGN-PC-04XZ20	http://www.angenechemical.com/productshow/AGN-PC-04XZ20.html
BLD Pharm	BD132435	http://www.bldpharm.com/products/29110-47-2.html
BioChemPartner	BCP09647	http://www.biochempartner.com/29110-47-2-BCP09647
BioCrick	BCC5180	http://www.biocrick.com/Guanfacine-BCC5180.html
BioSynth	J-017394	https://www.biosynth.com/en/products/all-products/products/J-017394.html
CSNpharm	CSN11127	https://www.csnpharm.com/products/guanfacine.html
Chem Scene	CS-2787	http://www.chemscene.com/29110-47-2.html
Clearsynth	CS-T-25721	https://www.clearsynth.com/en/CST25721.html
DC Chemicals	DC23226	http://www.dcchemicals.com/product_show-DC23226.html
Finetech	FT-0669068	http://www.finetechnology-ind.com/prod/detail/pub/1189924-28-4.html
Finetech	FT-0669067	http://www.finetechnology-ind.com/prod/detail/pub/29110-47-2.html
Hairui	HR141314	http://www.hairuichem.com/en/product/29110-47-2.html
Lab Network	LN01308386	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01308386
MedChem Express	HY-17416A	https://www.medchemexpress.com/guanfacine.html
Molcore	MC546722	https://www.molcore.com/product/29110-47-2
MuseChem	I003012	https://www.musechem.com/product/I003012.html
Smolecule	S576275	https://www.smolecule.com/products/s576275
Smolecule	S905071	https://www.smolecule.com/products/s905071
THE BioTek	bt-305246	https://www.thebiotek.com/product/others/bt-305246
Yuhao Chemical	RT3442	http://www.chemyuhao.com/29110-47-2.html

PubMed

Title	Date	PubMed
Guanfacine and secondary mania in children.	1999 Aug	10467976
Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension?	2001	14728014
Respiratory pattern and hypoxic ventilatory response in mice functionally lacking alpha2A-adrenergic receptors.	2001	11729878
Effects of alpha(2)-adrenergic agonists on lipopolysaccharide-induced aqueous flare elevation in pigmented rabbits.	2001 May-Jun	11369369
Presynaptic autoregulation of norepinephrine release from the sympathetic nerve fibers in the pineal gland of the domestic pig. Pharmacological characterization of alpha(2)adrenoceptors mediating this process.	2002 Apr	12019363
Testosterone dependence of salt-induced hypertension in Sabra rats and role of renal alpha(2)-adrenoceptor subtypes.	2002 Jan	11752095
Epidemiology and toxicity of pediatric guanfacine exposures.	2002 Nov	12398562
Stimulation of interleukin-12 production in mouse macrophages via activation of p38 mitogen-activated protein kinase by alpha2-adrenoceptor agonists.	2003 Apr 25	12706479
Hallucinations associated with initiation of guanfacine.	2003 Dec	14627872
Growth hormone response to guanfacine in boys with attention deficit hyperactivity disorder: a preliminary study.	2003 Fall	14642016
An antihypokinesic action of alpha2-adrenoceptors upon MPTP-induced behaviour deficits in mice.	2003 Feb	12589577
Pharmacological characterization of unique prazosin-binding sites in human kidney.	2003 Jul	12827214
Pharmacotherapy of pervasive developmental disorders in children and adolescents.	2004	15584771
The alpha(2A)-adrenergic agonist guanfacine improves visuomotor associative learning in monkeys.	2004 Jan	12931141
[Centrally-acting antihypertensive drugs].	2004 Mar	15171442
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	14999075
Potential noradrenergic targets for cognitive enhancement in schizophrenia.	2004 May	15115947
Methylphenidate an effective treatment for ADHD?	2004 Oct	15628613
Pulse-synchronous sympathetic burst power as a new index of sympathoexcitation in patients with heart failure.	2004 Oct	15178546
Alpha2 adrenergic agonists for the management of opioid withdrawal.	2004 Oct 18	15495025
Alpha-2 adrenoceptor activation inhibits phencyclidine-induced deficits of spatial working memory in rats.	2005 Aug	15714223
Aripiprazole in children and adolescents: clinical experience.	2005 Jul	16159529
The safety of non-stimulant agents for the treatment of attention-deficit hyperactivity disorder.	2005 Mar	15794722
Central sympathetic inhibition augments sleep-related ultradian rhythm of parasympathetic tone in patients with chronic heart failure.	2005 Sep	16127185
Mechanism of action of agents used in attention-deficit/hyperactivity disorder.	2006	16961428
Tourette's Syndrome.	2006 Jun	16650718
Syncope in children with Tourette's syndrome treated with guanfacine.	2006 Mar	16229000
Differential noradrenergic influence on seizure expression in genetically Fast and Slow kindling rat strains during massed trial stimulation of the amygdala.	2007 Feb	17027042

Patents

Sample Use Guides

In Vivo Use Guide

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 `Wed Jul 05 22:44:04 UTC 2023` Edited by `admin` on `Wed Jul 05 22:44:04 UTC 2023`
Record UNII	30OMY4G3MK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GUANFACINE

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