GUANETHIDINE

US Previously Marketed

First approved in 1960

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H22N4
Molecular Weight	198.3085
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=N)NCCN1CCCCCCC1

InChI

InChIKey=ACGDKVXYNVEAGU-UHFFFAOYSA-N

InChI=1S/C10H22N4/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14/h1-9H2,(H4,11,12,13)

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/cons/guanethidine.html

Guanethidine belongs to the general class of medicines called antihypertensives. It was used to treat high blood pressure (hypertension). It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues. It is taken up by norepinephrine transporters. It becomes concentrated in NE transmitter vesicles, replacing NE in these vesicles.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Norepinephrine transporter 197 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11403930	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: https://www.drugs.com/cons/guanethidine.html	Primary		Approved 8583	ISMELIN Approved Use Unknown Launch Date 1960

AUC

Value	Dose	Analyte	Population
2.68 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/374089/	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GUANETHIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.06 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/374089/	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GUANETHIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/374089/	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GUANETHIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.5 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/374089/	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:		GUANETHIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
650 mg single, oral Studied dose Dose: 650 mg Route: oral Route: single Dose: 650 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1104667	unhealthy, 43 years Health Status: unhealthy Age Group: 43 years Sources: https://pubmed.ncbi.nlm.nih.gov/1104667	Sources: https://pubmed.ncbi.nlm.nih.gov/1104667
75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/541046	unhealthy, 69 years Health Status: unhealthy Age Group: 69 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/541046	Disc. AE: Bradycardia... AEs leading to discontinuation/dose reduction: Bradycardia (extreme, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/541046
30 mg single, intravenous Dose: 30 mg Route: intravenous Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1802491	unhealthy Health Status: unhealthy Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/1802491	Disc. AE: Thrombophlebitis, Ischaemia... AEs leading to discontinuation/dose reduction: Thrombophlebitis (1 patient) Ischaemia (acute, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/1802491

AEs

AE	Significance	Dose	Population
Bradycardia	extreme, 1 patient Disc. AE	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/541046	unhealthy, 69 years Health Status: unhealthy Age Group: 69 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/541046
Thrombophlebitis	1 patient Disc. AE	30 mg single, intravenous Dose: 30 mg Route: intravenous Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1802491	unhealthy Health Status: unhealthy Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/1802491
Ischaemia	acute, 1 patient Disc. AE	30 mg single, intravenous Dose: 30 mg Route: intravenous Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1802491	unhealthy Health Status: unhealthy Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/1802491

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
FMO 7 BSEP 550 CYP1A2 2153 CYP2A6 879 CYP2C19 2057 CYP2E1 1060	FMO 34

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzY1In19	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzY1In19	no [IC50 >10 uM]
BSEP 554	inhibitor 4027 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50239969, https://dmd.aspetjournals.org/content/40/12/2332	no [IC50 >1000 uM]
CYP3A4 2633	inducer 1966 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000055652	yes
FMO 7	inhibitor 4027 Sources: https://www.sciencedirect.com/science/article/pii/000629529090009A?via%3Dihub	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
FMO 34	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/2894440/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzY1In19

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:51016	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:51016
ChemicalBook	CB3200665	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3200665
eMolecules	730852	https://www.emolecules.com/cgi-bin/more?vid=730852
MolPort	MolPort-003-666-197	https://www.molport.com/shop/molecule-link/MolPort-003-666-197
MolPort	MolPort-042-675-865	https://www.molport.com/shop/molecule-link/MolPort-042-675-865

PubMed

Title	Date	PubMed
Factors predisposing to postural hypotensive symptoms in the treatment of high blood pressure.	1975 Oct	127594
Relaxation of canine gallbladder to nerve stimulation involves adrenergic and non-adrenergic non-cholinergic mechanisms.	2001 Dec	11903916
Characterisation of a modified approach to the study of sympathetic neurotransmission and its presynaptic modulation in the isolated rabbit thoracic aorta.	2001 Nov-Dec	12183190
[Colorful pain].	2002	12463005
Effects of ecabet sodium, an antiulcer drug, on gastric adaptive relaxation in isolated guinea-pig stomachs.	2002	12224376
Influence of Helicobacter pylori infection on in vitro responsiveness of gastric fundus to agonists and to stimulation of enteric nerves in Mongolian gerbils.	2002	12203073
Intravenous regional guanethidine blockade in the treatment of post-traumatic complex regional pain syndrome type 1 (algodystrophy) of the hand.	2002 Apr	12002497
Rebound contraction by nitric oxide in the longitudinal muscle of porcine gastric fundus.	2002 Aug	12233818
Pharmacology and thermosensitivity of the dartos muscle isolated from rat scrotum.	2002 Aug	12163353
Excitatory motor innervation in the canine rectoanal region: role of changing receptor populations.	2002 Dec	12466242
Involvement of peptide histidine isoleucine in non-adrenergic non-cholinergic relaxation of the rat gastric fundus induced by high-frequency neuronal firing.	2002 Dec	12444500
Effect of cannabinoids on neural transmission in rat gastric fundus.	2002 Jan	11911227
Effects of guanethidine administration on compensatory ovarian hypertrophy, compensatory ovulation and follicular development in the prepubertal female guinea pig.	2002 Jul	12225770
Effects of functional peripheral sympathetic denervation induced by guanethidine on follicular development and ovulation of the adult female guinea pig.	2002 Jul	12225769
Bradykinin is involved in hyperalgesia induced by Bothrops jararaca venom.	2002 Jul	12076660
The effect of chemical sympathectomy on the conducting system of the white rat vagus nerve.	2002 Jul-Aug	12469610
Sympatholytic therapy in primary hypertension: a user friendly role for the future.	2002 Mar	11986908
Evidence of angiotensin II involvement in prolactin secretion in response to hemorrhage in adrenodemedullated and guanethidine-treated rats.	2002 Mar	11888852
Laryngeal effects of stimulation of rostral and ventral pons in the anaesthetized rat.	2002 May 3	11955472
The beneficial effects of protein tyrosine kinase inhibition on the circulatory failure induced by endotoxin in the rat.	2002 Nov	12412625
The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens.	2002 Nov	12401623
[Pharmacological sympathetic block in complex regional pain syndrome].	2002 Nov-Dec	12645391
[Therapeutic approach to complex regional pain syndrome].	2002 Nov-Dec	12645389
Purines and pyrimidines are not involved in NANC relaxant responses in the rabbit vaginal wall.	2002 Oct	12359633
Anesthetic pain management in Siriraj Hospital: a retrospective review.	2002 Sep	12452222
Additional evidence that the sympathetic nervous system regulates the vessel wall release of tissue plasminogen activator.	2002 Sep	12192298
Cholinergic and nitrergic regulation of in vivo giant migrating contractions in rat colon.	2002 Sep	12181166
Distribution of vasoactive intestinal polypeptide in the rat heart: effect of guanethidine and capsaicin.	2003 Apr	12725439
Effects of NCX 4050, a new NO donor, in rabbit and human corpus cavernosum.	2003 Apr	12641828
Ketamine and midazolam differentially inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits: role of superoxide anion and nitric oxide synthase.	2003 Feb	12552205
Functional evidence for a role of GABA receptors in modulating nerve activities of circular smooth muscle from rat colon in vitro.	2003 Feb 14	12535716
[Diagnose Sudeck's disease in good time and save your patient from martyrdom].	2003 Feb 27	12666531
Involvement of a purinergic pathway in the sympathetic regulation of motility in rat ileum.	2003 Feb 28	12559198
Neural mechanism of acupuncture-induced gastric relaxations in rats.	2003 Jan	12645791
Pharmacological evidence that tetraethylammonium-sensitive, iberiotoxin-insensitive K+ channels function as a negative feedback element for sympathetic neurotransmission by suppressing omega-conotoxin-GVIA-insensitive Ca2+ channels in the relaxation of rabbit facial vein.	2003 Jan	12616339
Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter.	2003 Jan	12522083
Influence of nitric oxide on neurogenic contraction and relaxation of the human gastroepiploic artery.	2003 Jan	12517679
Mechanisms of excitatory transmission in circular smooth muscles of the guinea pig seminal vesicle.	2003 Jan	12478197
Study of the mechanisms involved in the bradykinin-induced contraction of the pig iris sphincter muscle in vitro.	2003 Jan 1	12498923
Role of opioid and nitric oxide systems in the nonadrenergic noncholinergic-mediated relaxation of corpus cavernosum in bile duct-ligated rats.	2003 Jan 24	12559382
Prejunctional modulation of non-adrenergic non-cholinergic (NANC) inhibitory responses in the isolated guinea-pig gastric fundus.	2003 Jun	12787339
Cytosolic Ca2+ and phosphoinositide hydrolysis linked to constitutively active alpha 1D-adrenoceptors in vascular smooth muscle.	2003 Jun	12626653
Involvement of sympathetic efferents but not capsaicin-sensitive afferents in nociceptin-mediated dual control of rat synovial blood flow.	2003 Jun	12573980
Investigation of the mechanism of nicotine-induced relaxation in guinea pig gallbladder.	2003 Mar	12697411
Chemical sympathectomy-induced changes in TH-, VIP-, and CGRP-immunoreactive fibers in the rat mandible periosteum: influence on bone resorption.	2003 Mar	12548553
Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by alpha2-adrenoceptors in the presence of experimental colitis.	2003 May	12770936
Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants.	2003 May	12727271
Intrinsic regulation of CGRP release by dental pulp sympathetic fibers.	2003 May	12709509
Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats.	2003 May	12676748
Physiological regulation and NO-dependent inhibition of migrating myoelectric complex in the rat small bowel by OXA.	2003 Oct	12816759

Patents

Sample Use Guides

In Vivo Use Guide

For high blood pressure: Adults—at first, 10 or 12.5 milligrams (mg) once a day. Then, your doctor may increase your dose to 25 to 50 mg once a day. Children: the dose is based on body weight and must be determined by your doctor. The usual dose is 200 micrograms (mcg) per kilogram (kg) (90.9 mcg per pound) of body weight a day.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

GUANETHIDINE [HSDB]

Preferred Name

English

GUANETHIDINE

Official Name

English

(2-(HEXAHYDRO-1(2H)-AZOCINYL)ETHYL)GUANIDINE

Systematic Name

English

GUANETHIDINE [MI]

Common Name

English

Guanethidine [WHO-DD]

Common Name

English

GUANETHIDINE [VANDF]

Common Name

English

guanethidine [INN]

Common Name

English

GUANIDINE, (2-(HEXAHYDRO-1(2H)-AZOCINYL)ETHYL)-

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

S01EX01