METHOXAMINE HYDROCHLORIDE

US Previously Marketed

First approved in 1949

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H17NO3.ClH
Molecular Weight	247.719
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=YGRFXPCHZBRUKP-WJRQTEJMSA-N

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

HIDE SMILES / InChI

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
Effect of the blood substitute diaspirin crosslinked hemoglobin in rat mesenteric and human radial collateral arteries.	2001 Apr	11300652
Noradrenaline stimulates 5-hydroxytryptamine release from mouse ileal tissues via alpha(2)-adrenoceptors.	2001 Dec 7	11740950
Alpha-vascular responses after short-term and long-term inhibition of nitric oxide synthesis.	2001 Feb	11209996
Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats.	2001 Feb 2	11166291
Female gender does not influence the magnitude of ibutilide-induced repolarization delay and incidence of torsades de pointes in an in vivo rabbit model of the acquired long QT syndrome.	2001 Jul	11584331
Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive and control rats.	2001 Mar	11231951
Female gender is a risk factor for drug-induced long QT and cardiac arrhythmias in an in vivo rabbit model.	2001 May	11386514
Hypoxia alters the sensitivity of the L-type Ca(2+) channel to alpha-adrenergic receptor stimulation in the presence of beta-adrenergic receptor stimulation.	2001 May 25	11375273
Structure-activity relationships of diadenosine polyphosphates (Ap(n)As), adenosine polyphospho guanosines (Ap(n)Gs) and guanosine polyphospho guanosines (Gp(n)Gs) at P2 receptors in the rat mesenteric arterial bed.	2001 Nov	11682456
The noradrenergic inhibition of an apamin-sensitive, small-conductance Ca2+-activated K+ channel in hypothalamic gamma-aminobutyric acid neurons: pharmacology, estrogen sensitivity, and relevance to the control of the reproductive axis.	2001 Oct	11561059
Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation.	2001 Sep	11509525
Abrogation of alpha-adrenergic vasoactivity in chronically inflamed rat knee joints.	2001 Sep	11506997
[Priapism secondary to chronic myeloid leukemia: value of initial treatment with cavernous lavage plus adjuvant methoxamine].	2002 Apr	12068767
Male-female differences in the relative contribution of endothelial vasodilators released by rat tail artery.	2002 Aug 23	12137910
Dual adrenergic control of in vivo choline levels in the mouse major salivary glands.	2002 Feb	12423423
Types of adrenoreceptors mediating responses of rabbit gastric muscularis mucosae.	2002 Feb	11855551
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
Impairment of autoregulation following cortical venous occlusion in the rat.	2002 Mar	11877906
Mechanism underlying gamma-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats.	2002 Mar 1	11906718
ANP potentiates nonarterial baroreflex bradycardia: evidence from sinoaortic denervation in rats.	2002 May 31	12132649
Beta-adrenoceptor-induced inhibition of rat splenocyte proliferation: cytokine gene transcription as the target of action.	2002 Oct	12437066
Effects of in vivo lipopolysaccharide infusion on vasoconstrictor function of rat isolated mesentery, kidney, and aorta.	2003 Aug	12730359
Guanylyl cyclase receptors mediate cardiopulmonary vagal reflex actions of ANP.	2003 Feb	12574095
Acute vascular effects of the selective estrogen receptor modulator EM-652 (SCH 57068) in the rat mesenteric vascular bed.	2003 Feb	12566126
Stability of actin cytoskeleton and PKC-delta binding to actin regulate NKCC1 function in airway epithelial cells.	2003 Feb	12388079
Hormonal influence on expression and functionality of alpha1-adrenoceptor in rat submandibular gland.	2003 Jan 31	12531395
Role of the eNOS Glu298Asp variant on the GNB3825T allele dependent determination of alpha-adrenergic coronary constriction.	2003 May	12724620
Influence of caveolin on constitutively activated recombinant eNOS: insights into eNOS dysfunction in BDL rat liver.	2003 Sep	12829439
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.

Name

Type

Language

METHOXAMINE HYDROCHLORIDE

Common Name

English

BENZENEMETHANOL, .ALPHA.-((1S)-1-AMINOETHYL)-2,5-DIMETHOXY-, (.ALPHA.R)-, HYDROCHLORIDE

Common Name

English

METHOXAMINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

METHOXAMINE HYDROCHLORIDE [MI]

Common Name

English

VASOXYL

Brand Name

English

METHOXAMINE HYDROCHLORIDE [MART.]

Common Name

English

NSC-757102

Code

English

METHOXAMINE HYDROCHLORIDE [VANDF]

Common Name

English

(±)-.ALPHA.-(1-AMINOETHYL)-2,5-DIMETHOXYBENZYL ALCOHOL HYDROCHLORIDE

Systematic Name

English

Methoxamine hydrochloride [WHO-DD]

Common Name

English

METHOXAMINE HYDROCHLORIDE [JAN]

Common Name

English

METHOXAMINE HYDROCHLORIDE [HSDB]

Common Name

English

METHOXAMINE HCL

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29709