GUANABENZ ACETATE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H8Cl2N4.C2H4O2
Molecular Weight	291.134
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)=O.NC(=N)N\N=C\C1=C(Cl)C=CC=C1Cl

InChI

InChIKey=MCSPBPXATWBACD-GAYQJXMFSA-N

InChI=1S/C8H8Cl2N4.C2H4O2/c9-6-2-1-3-7(10)5(6)4-13-14-8(11)12;1-2(3)4/h1-4H,(H4,11,12,14);1H3,(H,3,4)/b13-4+;

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74517_Guanabenz%20Acetate_Prntlbl.pdf

Guanabenz, an antihypertensive agent for oral administration-, is an aminoguanidine derivative, 2,'6-dichlorobenzylideneamina-guanidine acetate. It is white to an almost white powder having not more than a slight odor. Sparingly soluble in water and in 0.1 N hydrochloric acid; soluble in alcohol and in propylene glycol. Guanabenz is an orally active central alpha-2 adrenergic agonist. Its antihypertensive action appears to be mediated via stimulation of central alpha-adrenergic receptors, resulting in a decrease of sympathetic outflow from the brain at the bulbar level to the peripheral circulatory system. In clinical trials, guanabenz acetate, given orally to hypertensive patients, effectively controlled blood pressure without any significant effect on glomerular filtration rate, renal blood flow, body fluid volume or body weight. The Myelin Repair Foundation and the National Institutes of Health (National Institute of Neurological Disorders and Stroke) are developing guanabenz for the treatment of multiple sclerosis. Unlike the currently available treatment for multiple sclerosis that suppresses the immune system, guanabenz, an FDA approved the drug for the treatment of high blood pressure, has a potential to reduce the loss of myelin by protecting and repairing myelin-producing cells in the brain from damage. Phase I development is underway in the US.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor alpha-2 113 Target ID: CHEMBL2093864 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6142954	Agonist 2678		1.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74517_Guanabenz%20Acetate_Prntlbl.pdf	Primary		Approved 8429	WYTENSIN Approved Use INDICATIONS AND USAGE. Guanabenz acetate tablets are indicated in the treatment of hypertension. It may be employed alone or in combination with a thiazide diuretic. Launch Date 1982
Multiple sclerosis 104 Sources: https://clinicaltrials.gov/ct2/show/NCT02423083	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6084122/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:		GUANABENZ plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6084122/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:		GUANABENZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
19 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6084122/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:		GUANABENZ plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
97 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6084122/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:		GUANABENZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6084122/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:		GUANABENZ plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6084122/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:		GUANABENZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
11% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6084122/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:		GUANABENZ plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6084122/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:		GUANABENZ plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
16 mg single, oral Recommended Dose: 16 mg Route: oral Route: single Dose: 16 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6084122 Page: p.S767	healthy, 22-55 Health Status: healthy Age Group: 22-55 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6084122 Page: p.S767	Sources: https://pubmed.ncbi.nlm.nih.gov/6084122 Page: p.S767
32 mg single, oral Highest studied dose Dose: 32 mg Route: oral Route: single Dose: 32 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	unhealthy, 39-65 n = 12 Health Status: unhealthy Condition: hypertension Age Group: 39-65 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764
16 mg single, oral Recommended Dose: 16 mg Route: oral Route: single Dose: 16 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	unhealthy, 39-65 n = 12 Health Status: unhealthy Condition: hypertension Age Group: 39-65 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	Disc. AE: Hypotension... Other AEs: Drowsiness... AEs leading to discontinuation/dose reduction: Hypotension (8.35%) Other AEs: Drowsiness (50%) Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764
24 mg single, oral Recommended Dose: 24 mg Route: oral Route: single Dose: 24 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	unhealthy, 39-65 n = 12 Health Status: unhealthy Condition: hypertension Age Group: 39-65 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	Disc. AE: Hypotension... AEs leading to discontinuation/dose reduction: Hypotension (8.35%) Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764
240 mg single, oral (max) Overdose Dose: 240 mg Route: oral Route: single Dose: 240 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787	healthy, 45 n = 1 Health Status: healthy Age Group: 45 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787	Other AEs: Sinus bradycardia... Other AEs: Sinus bradycardia Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787
480 mg single, oral (max) Overdose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788	unknown n = 3 Health Status: unknown Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788	Other AEs: Somnolence, Coma... Other AEs: Somnolence Coma Hypotension Bradycardia Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788

AEs

AE	Significance	Dose	Population
Drowsiness	50%	16 mg single, oral Recommended Dose: 16 mg Route: oral Route: single Dose: 16 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	unhealthy, 39-65 n = 12 Health Status: unhealthy Condition: hypertension Age Group: 39-65 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764
Hypotension	8.35% Disc. AE	16 mg single, oral Recommended Dose: 16 mg Route: oral Route: single Dose: 16 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	unhealthy, 39-65 n = 12 Health Status: unhealthy Condition: hypertension Age Group: 39-65 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764
Hypotension	8.35% Disc. AE	24 mg single, oral Recommended Dose: 24 mg Route: oral Route: single Dose: 24 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764	unhealthy, 39-65 n = 12 Health Status: unhealthy Condition: hypertension Age Group: 39-65 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/6084121 Page: p.S764
Sinus bradycardia		240 mg single, oral (max) Overdose Dose: 240 mg Route: oral Route: single Dose: 240 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787	healthy, 45 n = 1 Health Status: healthy Age Group: 45 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787
Bradycardia		480 mg single, oral (max) Overdose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788	unknown n = 3 Health Status: unknown Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788
Coma		480 mg single, oral (max) Overdose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788	unknown n = 3 Health Status: unknown Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788
Hypotension		480 mg single, oral (max) Overdose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788	unknown n = 3 Health Status: unknown Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788
Somnolence		480 mg single, oral (max) Overdose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788	unknown n = 3 Health Status: unknown Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/3994191 Page: p.787-788

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054 CYP1A1 349

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19754423/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9351903/	yes

Sourcing

Vendor/Aggregator	ID	URL
Chemspace	CSC030597450
Enamine	BBV-109684320
KeyOrganics	KS-1362
MolPort	MolPort-020-323-602
MolPort	MolPort-036-931-797
Otava	7322699
ZINC	ZINC000012503139	http://zinc15.docking.org/substances/ZINC000012503139
eMolecules	181669987
eMolecules	300500380

PubMed

Title	Date	PubMed
Pharmacological characterization of spinal alpha adrenoceptors related to blood pressure control in rats.	1987 Jan	2879903
Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking.	2000 Aug	10882840
Alpha-2 agonists induce amnesia through activation of the Gi-protein signalling pathway.	2004	15207363
Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype.	2004 Aug 31	15265636
Different response of ANP secretion to adrenoceptor stimulation in renal hypertensive rat atria.	2008 Jul	18378355
Human and mouse trace amine-associated receptor 1 have distinct pharmacology towards endogenous monoamines and imidazoline receptor ligands.	2009 Oct 23	19725810
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
Inhibitors of eIF2α dephosphorylation slow replication and stabilize latency in Toxoplasma gondii.	2013 Apr	23380722
Guanabenz interferes with ER stress and exerts protective effects in cardiac myocytes.	2014	24892553

Patents

Sample Use Guides

In Vivo Use Guide

Dosage with guanabenz acetate tablets should be individualized. A starling dose of 4 mg twice a day is recommended, whether guanabenz acetate tablets are used alone or with a thiazide diuretic. Dosage may be increased in increments of 4 to 8 mg per day every one to two weeks, depending on the patient's response. The maximum dose studied to date has been 32 mg twice daily, but doses as high as this are rarefy needed.

Route of Administration: Oral

In Vitro Use Guide

Peptidylprolyl isomerase B (cyclophilin B) mRNA expression levels were monitored after treatment of with hsiRNA (2 --500 nM) and increasing amounts of Guanabenz (0-100mkM) in HeLa cell culture for 24 h. Guanabenz acetate is capable of markedly increasing the cellular internalization and target mRNA silencing of hydrophobically modified siRNAs (hsiRNAs), yielding a ∼100-fold decrease in hsiRNA IC50 (from 132 nM to 2.4 nM).

Name

Type

Language

GUANABENZ ACETATE

Official Name

English

Guanabenz acetate [WHO-DD]

Common Name

English

GUANABENZ MONOACETATE

Common Name

English

[(2,6-Dichlorobenzylidene)amino]guanidine monoacetate

Systematic Name

English

WYTENSIN

Brand Name

English

GUANABENZ ACETATE [USP MONOGRAPH]

Common Name

English

GUANABENZ ACETATE [USAN]

Common Name

English

2-((2,6-DICHLOROPHENYL)METHYLENE)HYDRAZINECARBOXIMIDAMIDE MONOACETATE

Systematic Name

English

GUANABENZ ACETATE [USP-RS]

Common Name

English

GUANABENZ ACETATE [JAN]

Common Name

English

GUANABENZ ACETATE [VANDF]

Common Name

English

GUANABENZ ACETATE [HSDB]

Common Name

English

HYDRAZINECARBOXIMIDAMIDE, 2-((2,6-DICHLOROPHENYL)METHYLENE)-, MONOACETATE

Systematic Name

English

WY-8678 ACETATE

Code

English

GUANABENZ ACETATE [MART.]

Common Name

English

NSC-757044

Code

English

N-(2,6-DICHLOROBENZYLIDENE)-N'-AMIDINOHYDRAZINE MONOACETATE

Systematic Name

English

GUANABENZ MONOACETATE [MI]

Common Name

English

GUANABENZ ACETATE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29709