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

Details

Stereochemistry ACHIRAL
Molecular Formula C8H8Cl2N4
Molecular Weight 231.0821
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of GUANABENZ

SMILES

c1cc(c(/C(/[H])=N/NC(=N)N)c(c1)Cl)Cl

InChI

InChIKey=WDZVGELJXXEGPV-YIXHJXPBSA-N
InChI=1S/C8H8Cl2N4/c9-6-2-1-3-7(10)5(6)4-13-14-8(11)12/h1-4H,(H4,11,12,14)/b13-4+

HIDE SMILES / InChI
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.7 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

4.00204792E11
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.4 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
19 ng × h/mL
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.3 h
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
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
11%
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%
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

Doses

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

AEs

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

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim

Drug as victim

PubMed

PubMed

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

Sample Use Guides

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
INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
GUANABENZ [MI]
Common Name English
GUANABENZ [WHO-DD]
Common Name English
NSC-68982
Code English
N-(2,6-DICHLOROBENZYLIDENE)-N'-AMIDINOHYDRAZINE
Systematic Name English
GUANABENZ [INN]
Common Name English
((2,6-DICHLOROBENZYLIDENE)AMINO)GUANIDINE
Systematic Name English
2-((2,6-DICHLOROPHENYL)METHYLENE)HYDRAZINECARBOXIMIDAMIDE
Systematic Name English
WY-8678
Code English
GUANABENZ [VANDF]
Common Name English
GUANABENZ [USAN]
Common Name English
HYDRAZINECARBOXIMIDAMIDE, 2-((2,6-DICHLOROPHENYL)METHYLENE)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C29709
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
NDF-RT N0000175554
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
LIVERTOX 472
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
EU-Orphan Drug EU/3/09/625
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
NDF-RT N0000009918
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
Code System Code Type Description
INN
3108
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
MERCK INDEX
M5863
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
3952
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
ChEMBL
CHEMBL420
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
LACTMED
Guanabenz
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
PUBCHEM
5702063
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
NCI_THESAURUS
C83740
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
FDA UNII
GGD30112WC
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
CAS
5051-62-7
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
RXCUI
5033
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY RxNorm
EVMPD
SUB07978MIG
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
WIKIPEDIA
GUANABENZ
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
MESH
D006143
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
DRUG BANK
DB00629
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
IUPHAR
5443
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
EPA CompTox
5051-62-7
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY
ECHA (EC/EINECS)
225-750-8
Created by admin on Sat Jun 26 01:01:35 UTC 2021 , Edited by admin on Sat Jun 26 01:01:35 UTC 2021
PRIMARY