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 19 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 2678		4.86 null [pKi]
Alpha-1D adrenergic receptor 6 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 2678		1299.27 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Fecal incontinence 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00893607	Primary		Approved 8429	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 n = 24 Health Status: healthy Age Group: 18 - 60 years Sex: M+F Population Size: 24 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 n = 24 Health Status: healthy Age Group: 18 - 60 years Sex: M+F Population Size: 24 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
Microphysiometric analysis of human alpha1a-adrenoceptor expressed in Chinese hamster ovary cells.	1999 Jun	10433504
Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebo-controlled, double-blind crossover study.	2001	11135381
Effect of the blood substitute diaspirin crosslinked hemoglobin in rat mesenteric and human radial collateral arteries.	2001 Apr	11300652
Erection and NO override the vasoconstrictive effect of alpha-adrenergic stimulation in the rat penile vasculature.	2001 Aug	11494078
Role of tyrosine kinase activity in alpha-adrenergic inhibition of the beta-adrenergically regulated L-type Ca(2+) current in guinea-pig ventricular myocytes.	2001 Dec 15	11744754
Noradrenaline stimulates 5-hydroxytryptamine release from mouse ileal tissues via alpha(2)-adrenoceptors.	2001 Dec 7	11740950
Assessment of the pro-arrhythmic potential of anti-arrhythmic drugs: an experimental approach.	2001 Jan	11452340
d,l-sotalol enhances baroreflex sensitivity in conscious rats surviving acute myocardial infarction.	2001 Jul	11428905
Phe-308 and Phe-312 in transmembrane domain 7 are major sites of alpha 1-adrenergic receptor antagonist binding. Imidazoline agonists bind like antagonists.	2001 Jul 6	11331292
Increased heme oxygenase activity in splanchnic organs from portal hypertensive rats: role in modulating mesenteric vascular reactivity.	2001 Jun	11451163
The influence of phosphodiesterase inhibitor, rolipram, on hemodynamics in lipopolysaccharide-treated rats.	2001 Mar	11325016
Adrenergic nerves mediate acetylcholine-induced endothelium-independent vasodilation in the rat mesenteric resistance artery.	2001 May 11	11426846
Assessment of ventricular contractility during cardiac magnetic resonance imaging examinations using normalized maximal ventricular power.	2001 Nov	11791680
Attenuated agonist evoked vasoconstrictor responses in the perfused mesenteric vascular bed of streptozotocin diabetic rats.	2001 Nov	11682701
Effect of repeated treatment with reboxetine on the central alpha1-adrenergic system.	2001 Nov-Dec	11985343
Development of a rat model of sexual performance anxiety: effect of behavioural and pharmacological hyperadrenergic stimulation on APO-induced erections.	2002 Apr	11979326
A mitogen-activated protein kinase is involved in the inotropic but not chronotropic actions of adrenoceptor agonists and endothelin-1.	2002 Aug	12122507
Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes.	2002 Aug 9	12169649
(-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens.	2002 Dec 5	12450575
Purinergic modulation of vascular sympathetic neurotransmission.	2002 Jan	11855674
Blood-brain barrier breakdown in septic encephalopathy and brain tumours.	2002 Jun	12162731
Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension.	2002 Jun	12003815
Compression and expansion wavefront travel in canine ascending aortic flow: wave intensity analysis.	2002 Mar	12027238
Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors.	2002 Mar	11939713
Potential anaphylactic shock with abciximab readministration.	2002 Mar	11898893
Use of methoxamine in the resuscitation of epinephrine resistant electromechanical dissociation.	2002 Mar	11879218
Effects of chronic administration of L-arginine on vasoactive responses induced by endothelin-1 and its plasma level in streptozotocin-induced diabetic rats.	2002 Oct	12596889
Beta-adrenoceptor-induced inhibition of rat splenocyte proliferation: cytokine gene transcription as the target of action.	2002 Oct	12437066
Effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in perfused rat mesenteric arterial beds.	2003	12908683
Vasodilator actions of abnormal-cannabidiol in rat isolated small mesenteric artery.	2003 Apr	12711633
Deficit in nitric oxide production in cirrhotic rat livers is located in the sinusoidal and postsinusoidal areas.	2003 Apr	12490431
Evidence for the role of alpha1D- and alpha1A-adrenoceptors in contraction of the rat mesenteric artery.	2003 Feb	12646397
Stability of actin cytoskeleton and PKC-delta binding to actin regulate NKCC1 function in airway epithelial cells.	2003 Feb	12388079
L-Erythro-methoxamine is more potent than phenylephrine in effecting contraction of internal anal sphincter in vitro.	2003 Jul	12854116
Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers.	2003 Oct	12971960
Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis.	2003 Oct 6	14520469
Novel form of long-term synaptic depression in rat hippocampus induced by activation of alpha 1 adrenergic receptors.	2004 Feb	14573563

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 `Fri Dec 15 16:31:09 GMT 2023` Edited by `admin` on `Fri Dec 15 16:31:09 GMT 2023`
Record UNII	HUQ1KC1YLI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHOXAMINE

Official Name

English

NRL-001

Code

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