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

Molecular Formula	C11H17NO3
Molecular Weight	211.2576
Charge	0
Count

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

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Profound bradycardia and hypotension following spinal anaesthesia in a patient receiving an ACE inhibitor: an important 'drug' interaction?	1999 Nov	10713875
Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebo-controlled, double-blind crossover study.	2001	11135381
Nitric oxide modulates acetylcholine-induced vasodilatation in the hepatic arterial vasculature of the dual-perfused rat liver.	2001 Apr	11421856
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
Alpha-vascular responses after short-term and long-term inhibition of nitric oxide synthesis.	2001 Feb	11209996
Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects.	2001 Feb	11160067
Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats.	2001 Feb 2	11166291
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
Characterization of alpha1-adrenoceptor-mediated contraction in the mouse thoracic aorta.	2001 Jul 20	11476759
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
Regional haemodynamic responses to the cannabinoid agonist, WIN 55212-2, in conscious, normotensive rats, and in hypertensive, transgenic rats.	2001 Jun	11375262
The influence of phosphodiesterase inhibitor, rolipram, on hemodynamics in lipopolysaccharide-treated rats.	2001 Mar	11325016
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
MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau.	2001 Nov	11668061
Stimulation of alpha1-adrenoceptors inhibits memory consolidation in the chick.	2001 Oct	11703465
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
Alpha2-adrenoceptor ligands inhibit alpha1-adrenoceptor-mediated contraction of isolated rat arteries.	2002 Aug	12570016
Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes.	2002 Aug 9	12169649
Dual adrenergic control of in vivo choline levels in the mouse major salivary glands.	2002 Feb	12423423
Activation of alpha 1-adrenoceptors is not essential for the mediation of ischaemic preconditioning in rat heart.	2002 Jan-Feb	11906456
Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles.	2002 Jul 30	12147535
Blood-brain barrier breakdown in septic encephalopathy and brain tumours.	2002 Jun	12162731
Compression and expansion wavefront travel in canine ascending aortic flow: wave intensity analysis.	2002 Mar	12027238
Potential anaphylactic shock with abciximab readministration.	2002 Mar	11898893
ANP potentiates nonarterial baroreflex bradycardia: evidence from sinoaortic denervation in rats.	2002 May 31	12132649
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
Use of pharmaceuticals in noninvasive cardiovascular diagnosis.	2002 Sep-Oct	12350244
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
Effects of hypochlorite and hydrogen peroxide on cardiac autonomic receptors and vascular endothelial function.	2003 Apr	12680842
Effects of in vivo lipopolysaccharide infusion on vasoconstrictor function of rat isolated mesentery, kidney, and aorta.	2003 Aug	12730359
Evidence for the role of alpha1D- and alpha1A-adrenoceptors in contraction of the rat mesenteric artery.	2003 Feb	12646397
Guanylyl cyclase receptors mediate cardiopulmonary vagal reflex actions of ANP.	2003 Feb	12574095
Functional development of the rat urinary bladder after pre- or postpubertal castration.	2003 Feb	12566851
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
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 Mar	12733822
Role of the eNOS Glu298Asp variant on the GNB3825T allele dependent determination of alpha-adrenergic coronary constriction.	2003 May	12724620
Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers.	2003 Oct	12971960
Fish Balistes capriscus skin extract-induced relaxation in mesenteric arterial bed of rat.	2003 Oct	12963145
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 `Sat Dec 16 17:57:11 GMT 2023` Edited by `admin` on `Sat Dec 16 17:57:11 GMT 2023`
Record UNII	8MB4MJ9R7L
Record Status	`Validated (UNII)`
Record Version

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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