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 2637		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 2637		1299.27 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Fecal incontinence 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00893607	Primary		Approved 8307	Vasoxyl Approved Use Unknown Launch Date 3.78691191E11

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
Cyclosporin A: effects on the secretory process and noradrenergic activity in the submandibular gland of the rat.	2001	11752891
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
Antihypertensive drugs induce structural remodeling of the penile vasculature.	2001 Aug	11458127
Alpha-1A adrenoceptors modulate potentiation of spinal nociceptive pathways in the rat spinal cord in vitro.	2001 Dec	11684150
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
Increased heme oxygenase activity in splanchnic organs from portal hypertensive rats: role in modulating mesenteric vascular reactivity.	2001 Jun	11451163
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
Adrenergic nerves mediate acetylcholine-induced endothelium-independent vasodilation in the rat mesenteric resistance artery.	2001 May 11	11426846
Use of methoxamine in the resuscitation of epinephrine-resistant electromechanical dissociation.	2001 Nov	11703242
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
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
Development of a rat model of sexual performance anxiety: effect of behavioural and pharmacological hyperadrenergic stimulation on APO-induced erections.	2002 Apr	11979326
Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers.	2002 Aug	12143046
Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes.	2002 Aug 9	12169649
Mediation of contraction in rat cauda epididymidis by alpha-adrenoceptors.	2002 Dec	12530926
Calmodulin inhibitor W-7 unmasks a novel electrocardiographic parameter that predicts initiation of torsade de pointes.	2002 Feb 12	11839636
Purinergic modulation of vascular sympathetic neurotransmission.	2002 Jan	11855674
Interaction of nitric oxide with calcium in the mesenteric bed of bile duct-ligated rats.	2002 Jan	11815385
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
Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors.	2002 Mar	11939713
Modulation of Na-K-2Cl cotransport by intracellular Cl(-) and protein kinase C-delta in Calu-3 cells.	2002 May	11943682
Acute vascular effects of the selective estrogen receptor modulator EM-652 (SCH 57068) in the rat mesenteric vascular bed.	2003 Feb	12566126
The effects of volatile anesthetics on nonadrenergic, noncholinergic depressor responses in rats.	2003 Jan	12505937
Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers.	2003 Jan	12500202
Vasoconstrictor responsiveness of tail arteries from endotoxaemic rats.	2003 Jan 24	12559375
Hormonal influence on expression and functionality of alpha1-adrenoceptor in rat submandibular gland.	2003 Jan 31	12531395
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
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
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 20:23:28 UTC 2022` Edited by `admin` on `Fri Dec 16 20:23:28 UTC 2022`
Record UNII	HUQ1KC1YLI
Record Status	`Validated (UNII)`
Record Version

Download

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