METHOXAMINE

US Previously Marketed

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 2662		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 2662		1299.27 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Fecal incontinence 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00893607	Primary		Approved 8360	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
Effects of P5, a novel oxazolo(3,2-a)pyridine derivative with a long-acting antihypertensive activity, on different agonist-mediated pressor responses in pithed rats.	2001 Apr	11679017
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
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
Effect of high extracellular Ca(2+) levels in spontaneously hypertensive rat aorta.	2001 Dec 7	11740954
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
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
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
MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau.	2001 Nov	11668061
Abrogation of alpha-adrenergic vasoactivity in chronically inflamed rat knee joints.	2001 Sep	11506997
Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers.	2002 Aug	12143046
A mitogen-activated protein kinase is involved in the inotropic but not chronotropic actions of adrenoceptor agonists and endothelin-1.	2002 Aug	12122507
Pregnancy and acute baroreflex resetting in conscious rabbits.	2002 Aug	12121856
Chiral separation of methoxamine and lobeline in capillary zone electrophoresis using ethylbenzene-deactivated fused-silica capillary columns and cyclodextrins as buffer additives.	2002 Aug 1	12110384
Male-female differences in the relative contribution of endothelial vasodilators released by rat tail artery.	2002 Aug 23	12137910
Mediation of contraction in rat cauda epididymidis by alpha-adrenoceptors.	2002 Dec	12530926
Dual adrenergic control of in vivo choline levels in the mouse major salivary glands.	2002 Feb	12423423
Existence of functional alpha1A- and alpha1D- but no alpha1B-adrenoceptor subtypes in rat common carotid arteries.	2002 Feb	11928714
Types of adrenoreceptors mediating responses of rabbit gastric muscularis mucosae.	2002 Feb	11855551
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
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
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
Potential anaphylactic shock with abciximab readministration.	2002 Mar	11898893
Use of methoxamine in the resuscitation of epinephrine resistant electromechanical dissociation.	2002 Mar	11879218
Impairment of autoregulation following cortical venous occlusion in the rat.	2002 Mar	11877906
Structural factors increase blood pressure through the interaction of resistance vessel geometry with neurohumoral and local factors: estimates in rabbits with renal cellophane-wrap hypertension with intact effectors and during neurohumoral blockade.	2002 Mar	11875315
Mechanism underlying gamma-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats.	2002 Mar 1	11906718
Modulation of Na-K-2Cl cotransport by intracellular Cl(-) and protein kinase C-delta in Calu-3 cells.	2002 May	11943682
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
Effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in perfused rat mesenteric arterial beds.	2003	12908683
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
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
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 `Wed Jul 05 23:56:56 UTC 2023` Edited by `admin` on `Wed Jul 05 23:56:56 UTC 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