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 191 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11403930	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.drugs.com/cons/guanethidine.html	Primary		Approved 8429	ISMELIN Approved Use Unknown Launch Date 1960

AUC

Value	Dose	Analyte	Population
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
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
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

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 n = 1 Health Status: unhealthy Age Group: 43 years Population Size: 1 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 Co-administed with:: furosemide(40 mg twice daily) Sources: https://pubmed.ncbi.nlm.nih.gov/541046	unhealthy, 69 years n = 1 Health Status: unhealthy Condition: hypertension Age Group: 69 years Sex: M Population Size: 1 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 n = 120 Health Status: unhealthy Condition: algodystrophy Sex: M+F Population Size: 120 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 Co-administed with:: furosemide(40 mg twice daily) Sources: https://pubmed.ncbi.nlm.nih.gov/541046	unhealthy, 69 years n = 1 Health Status: unhealthy Condition: hypertension Age Group: 69 years Sex: M Population Size: 1 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 n = 120 Health Status: unhealthy Condition: algodystrophy Sex: M+F Population Size: 120 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 n = 120 Health Status: unhealthy Condition: algodystrophy Sex: M+F Population Size: 120 Sources: https://pubmed.ncbi.nlm.nih.gov/1802491

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
FMO 7 BSEP 402 CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882	FMO 35

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzY1In19	no [IC50 >10 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc2NSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzY1In19	no [IC50 >10 uM]
BSEP 403	inhibitor 3277 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 1925	inducer 1573 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000055652	yes
FMO 7	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/000629529090009A?via%3Dihub	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
FMO 35	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/2894440/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
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
eMolecules	730852	https://www.emolecules.com/cgi-bin/more?vid=730852

PubMed

Title	Date	PubMed
Factors predisposing to postural hypotensive symptoms in the treatment of high blood pressure.	1975 Oct	127594
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
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
Sympathetic-renal interaction in chronic arterial pressure control.	2002 Aug	12121857
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
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
Role of Ca2+-activated Cl- channels and MLCK in slow IJP in opossum esophageal smooth muscle.	2002 Jul	12065297
Alpha7-nicotinic acetylcholine receptors on cerebral perivascular sympathetic nerves mediate choline-induced nitrergic neurogenic vasodilation.	2002 Jul 12	12114323
Effects of GABA on circular smooth muscle spontaneous activities of rat distal colon.	2002 Jul 12	12084388
Chemical sympathectomy alters food intake and thermogenic responses to catecholamines in rats.	2002 Jul 5	12074938
The effect of chemical sympathectomy on the conducting system of the white rat vagus nerve.	2002 Jul-Aug	12469610
Intravenous regional blocks with guanethidine and prilocaine combined with physiotherapy: two children with complex regional pain syndrome, type 1.	2002 May	12095024
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

Official Name

English

GUANETHIDINE [HSDB]

Common 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