METHOXAMINE

US Previously Marketed

First approved in 1949

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H17NO3
Molecular Weight	211.2576
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(OC)C(=C1)[C@@H](O)[C@H](C)N

InChI

InChIKey=WJAJPNHVVFWKKL-CPCISQLKSA-N

InChI=1S/C11H17NO3/c1-7(12)11(13)9-6-8(14-2)4-5-10(9)15-3/h4-7,11,13H,12H2,1-3H3/t7-,11-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C11H17NO3
Molecular Weight	211.2576
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugbank.ca/drugs/DB00723 | https://www.ncbi.nlm.nih.gov/pubmed/7875228 | https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=006772 | https://www.ncbi.nlm.nih.gov/pubmed/29196668

Methoxamine is an alpha-adrenergic agonist that induces prolonged peripheral vasoconstriction, and can also stimulate the release of arginine vasopressin in humans. In clinical trials, methoxamine was found to improve fecal incontinence. It had been marketed by Glaxo-Smith-Kline under the brand name Vasoxyl but has been discontinued. Methoxamine was also found to stimulate the induction of hiPSC-derived hepatoblasts to ALBUMIN+ cells.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-1A adrenergic receptor 22 Target ID: P35348\|\|\|B0ZBD9\|\|\|Q6RUJ8 Gene ID: 148.0 Gene Symbol: ADRA1A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7875228	Agonist 2752		4.86 null [pKi]
Alpha-1D adrenergic receptor 9 Target ID: P25100 Gene ID: 146.0 Gene Symbol: ADRA1D Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19493707	Agonist 2752		1299.27 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Fecal incontinence 6 Sources: https://clinicaltrials.gov/ct2/show/NCT00893607	Primary		Approved 8583	Vasoxyl Approved Use Unknown Launch Date 1981

C_max

Value	Dose	Co-administered	Analyte	Population
15.69 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24499494/	10 mg single, rectal dose: 10 mg route of administration: Rectal experiment type: SINGLE co-administered:		METHOXAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
178.95 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24499494/	10 mg single, rectal dose: 10 mg route of administration: Rectal experiment type: SINGLE co-administered:		METHOXAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24499494/	10 mg single, rectal dose: 10 mg route of administration: Rectal experiment type: SINGLE co-administered:		METHOXAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
15 mg single, rectal Recommended Dose: 15 mg Route: rectal Route: single Dose: 15 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24499492/	healthy, 18 - 60 years Health Status: healthy Age Group: 18 - 60 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/24499492/	DLT: Heart rate decreased... Dose limiting toxicities: Heart rate decreased (8 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/24499492/

AEs

AE	Significance	Dose	Population
Heart rate decreased	8 patients DLT	15 mg single, rectal Recommended Dose: 15 mg Route: rectal Route: single Dose: 15 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24499492/	healthy, 18 - 60 years Health Status: healthy Age Group: 18 - 60 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/24499492/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6839	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6839
eMolecules	902115	https://www.emolecules.com/cgi-bin/more?vid=902115

PubMed

Title	Date	PubMed
Novel form of long-term synaptic depression in rat hippocampus induced by activation of alpha 1 adrenergic receptors.	2004-02	14573563
Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis.	2003-10-06	14520469
Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers.	2003-10	12971960
Fish Balistes capriscus skin extract-induced relaxation in mesenteric arterial bed of rat.	2003-10	12963145
Influence of caveolin on constitutively activated recombinant eNOS: insights into eNOS dysfunction in BDL rat liver.	2003-09	12829439
Effects of in vivo lipopolysaccharide infusion on vasoconstrictor function of rat isolated mesentery, kidney, and aorta.	2003-08	12730359
L-Erythro-methoxamine is more potent than phenylephrine in effecting contraction of internal anal sphincter in vitro.	2003-07	12854116
Role of the eNOS Glu298Asp variant on the GNB3825T allele dependent determination of alpha-adrenergic coronary constriction.	2003-05	12724620
Vasodilator actions of abnormal-cannabidiol in rat isolated small mesenteric artery.	2003-04	12711633
Effects of hypochlorite and hydrogen peroxide on cardiac autonomic receptors and vascular endothelial function.	2003-04	12680842
Deficit in nitric oxide production in cirrhotic rat livers is located in the sinusoidal and postsinusoidal areas.	2003-04	12490431
Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the alpha1-adrenoceptors.	2003-03	12733822
Evidence for the role of alpha1D- and alpha1A-adrenoceptors in contraction of the rat mesenteric artery.	2003-02	12646397
Guanylyl cyclase receptors mediate cardiopulmonary vagal reflex actions of ANP.	2003-02	12574095
Functional development of the rat urinary bladder after pre- or postpubertal castration.	2003-02	12566851
Acute vascular effects of the selective estrogen receptor modulator EM-652 (SCH 57068) in the rat mesenteric vascular bed.	2003-02	12566126
Stability of actin cytoskeleton and PKC-delta binding to actin regulate NKCC1 function in airway epithelial cells.	2003-02	12388079
Hormonal influence on expression and functionality of alpha1-adrenoceptor in rat submandibular gland.	2003-01-31	12531395
Vasoconstrictor responsiveness of tail arteries from endotoxaemic rats.	2003-01-24	12559375
The effects of volatile anesthetics on nonadrenergic, noncholinergic depressor responses in rats.	2003-01	12505937
Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers.	2003-01	12500202
Effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in perfused rat mesenteric arterial beds.	2003	12908683
(-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens.	2002-12-05	12450575
Mediation of contraction in rat cauda epididymidis by alpha-adrenoceptors.	2002-12	12530926
Effects of chronic administration of L-arginine on vasoactive responses induced by endothelin-1 and its plasma level in streptozotocin-induced diabetic rats.	2002-10	12596889
Beta-adrenoceptor-induced inhibition of rat splenocyte proliferation: cytokine gene transcription as the target of action.	2002-10	12437066
Use of pharmaceuticals in noninvasive cardiovascular diagnosis.	2002-09-28	12350244
Male-female differences in the relative contribution of endothelial vasodilators released by rat tail artery.	2002-08-23	12137910
Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes.	2002-08-09	12169649
Chiral separation of methoxamine and lobeline in capillary zone electrophoresis using ethylbenzene-deactivated fused-silica capillary columns and cyclodextrins as buffer additives.	2002-08-01	12110384
Alpha2-adrenoceptor ligands inhibit alpha1-adrenoceptor-mediated contraction of isolated rat arteries.	2002-08	12570016
Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers.	2002-08	12143046
A mitogen-activated protein kinase is involved in the inotropic but not chronotropic actions of adrenoceptor agonists and endothelin-1.	2002-08	12122507
Pregnancy and acute baroreflex resetting in conscious rabbits.	2002-08	12121856
Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles.	2002-07-30	12147535
Blood-brain barrier breakdown in septic encephalopathy and brain tumours.	2002-06	12162731
Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension.	2002-06	12003815
Strain-specific patterns of autonomic nervous system activity and heart failure susceptibility in mice.	2002-06	12003814
ANP potentiates nonarterial baroreflex bradycardia: evidence from sinoaortic denervation in rats.	2002-05-31	12132649
Effect of repeated treatment with reboxetine on the central alpha1-adrenergic system.	2002-05-03	11985343
Modulation of Na-K-2Cl cotransport by intracellular Cl(-) and protein kinase C-delta in Calu-3 cells.	2002-05	11943682
[Priapism secondary to chronic myeloid leukemia: value of initial treatment with cavernous lavage plus adjuvant methoxamine].	2002-04	12068767
Development of a rat model of sexual performance anxiety: effect of behavioural and pharmacological hyperadrenergic stimulation on APO-induced erections.	2002-04	11979326
Activation of alpha 1-adrenoceptors is not essential for the mediation of ischaemic preconditioning in rat heart.	2002-03-22	11906456
Mechanism underlying gamma-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats.	2002-03-01	11906718
Compression and expansion wavefront travel in canine ascending aortic flow: wave intensity analysis.	2002-03	12027238
Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors.	2002-03	11939713
Potential anaphylactic shock with abciximab readministration.	2002-03	11898893
Dual adrenergic control of in vivo choline levels in the mouse major salivary glands.	2002-02	12423423
Existence of functional alpha1A- and alpha1D- but no alpha1B-adrenoceptor subtypes in rat common carotid arteries.	2002-02	11928714

Patents

Sample Use Guides

In Vivo Use Guide

Patients suffering fecal incontinence were administered 10 mg of Methoxamine as a slow release suppository into the anal canal.

Route of Administration: Rectal

In Vitro Use Guide

Hepatic differentiation of hiPSC colonies grown on SNL feeder cells occurred in three culture stages over 18 - 21 days concluding with hepatocyte culture medium containing 20 ng/ml recombinant human hepatocyte growth factor and 20 ng/ml recombinant human Oncostatin M for 7 - 8 days. Methoxamine from a commercial compound screen was included in the stage 3 hepatocyte culture media. After 7 days incubation cells were subjected to anti-ALBUMIN immunostaining, and the number and induction rate of ALBUMIN+ cells was examined. Methoxamine was the sole effective compound among the 1,120 tested. The induction rate of hiPSC-derived hepatoblasts into ALBUMIN+ cells in the populations treated with methoxamine was 33.7%. Methoxamine was then titrated against hiPSC-derived hepatoblasts cultures across a range of 0.001 μM to 100 μM and demonstrated a dose-dependent induction activity with the highest efficiency at 1 μM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:30:15 GMT 2025` Edited by `admin` on `Mon Mar 31 18:30:15 GMT 2025`
Record UNII	HUQ1KC1YLI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NRL-001

Preferred Name

English

METHOXAMINE

Official Name

English

(1R*,2S*)-2-AMINO-1-(2,5-DIMETHOXYPHENYL)PROPAN-1-OL

Systematic Name

English

NRL001

Code

English

METHOXAMINE [MI]

Common Name

English

Methoxamine [WHO-DD]

Common Name

English

REL-(1R,2S)-2-AMINO-1-(2,5-DIMETHOXYPHENYL)PROPAN-1-OL, (±)-

Common Name

English

methoxamine [INN]

Common Name

English

METHOXAMINE [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C01CA10