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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 of METHOXAMINE

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

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P35348|||B0ZBD9|||Q6RUJ8
Gene ID: 148.0
Gene Symbol: ADRA1A
Target Organism: Homo sapiens (Human)
4.86 null [pKi]
Target ID: P25100
Gene ID: 146.0
Gene Symbol: ADRA1D
Target Organism: Homo sapiens (Human)
1299.27 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Vasoxyl

Approved Use

Unknown

Launch Date

3.78691191E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.69 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
178.95 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.15 h
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

Doses

DosePopulationAdverse events​
15 mg single, rectal
Recommended
Dose: 15 mg
Route: rectal
Route: single
Dose: 15 mg
Sources:
healthy, 18 - 60 years
n = 24
Health Status: healthy
Age Group: 18 - 60 years
Sex: M+F
Population Size: 24
Sources:
DLT: Heart rate decreased...
Dose limiting toxicities:
Heart rate decreased (8 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Heart rate decreased 8 patients
DLT
15 mg single, rectal
Recommended
Dose: 15 mg
Route: rectal
Route: single
Dose: 15 mg
Sources:
healthy, 18 - 60 years
n = 24
Health Status: healthy
Age Group: 18 - 60 years
Sex: M+F
Population Size: 24
Sources:
PubMed

PubMed

TitleDatePubMed
Cyclosporin A: effects on the secretory process and noradrenergic activity in the submandibular gland of the rat.
2001
Effect of the blood substitute diaspirin crosslinked hemoglobin in rat mesenteric and human radial collateral arteries.
2001 Apr
Erection and NO override the vasoconstrictive effect of alpha-adrenergic stimulation in the rat penile vasculature.
2001 Aug
Antihypertensive drugs induce structural remodeling of the penile vasculature.
2001 Aug
Alpha-1A adrenoceptors modulate potentiation of spinal nociceptive pathways in the rat spinal cord in vitro.
2001 Dec
Alpha-vascular responses after short-term and long-term inhibition of nitric oxide synthesis.
2001 Feb
Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects.
2001 Feb
Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats.
2001 Feb 2
Assessment of the pro-arrhythmic potential of anti-arrhythmic drugs: an experimental approach.
2001 Jan
d,l-sotalol enhances baroreflex sensitivity in conscious rats surviving acute myocardial infarction.
2001 Jul
Characterization of alpha1-adrenoceptor-mediated contraction in the mouse thoracic aorta.
2001 Jul 20
Increased heme oxygenase activity in splanchnic organs from portal hypertensive rats: role in modulating mesenteric vascular reactivity.
2001 Jun
Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive and control rats.
2001 Mar
Female gender is a risk factor for drug-induced long QT and cardiac arrhythmias in an in vivo rabbit model.
2001 May
Adrenergic nerves mediate acetylcholine-induced endothelium-independent vasodilation in the rat mesenteric resistance artery.
2001 May 11
Use of methoxamine in the resuscitation of epinephrine-resistant electromechanical dissociation.
2001 Nov
Attenuated agonist evoked vasoconstrictor responses in the perfused mesenteric vascular bed of streptozotocin diabetic rats.
2001 Nov
Effect of repeated treatment with reboxetine on the central alpha1-adrenergic system.
2001 Nov-Dec
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
Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation.
2001 Sep
Development of a rat model of sexual performance anxiety: effect of behavioural and pharmacological hyperadrenergic stimulation on APO-induced erections.
2002 Apr
Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers.
2002 Aug
Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes.
2002 Aug 9
Mediation of contraction in rat cauda epididymidis by alpha-adrenoceptors.
2002 Dec
Calmodulin inhibitor W-7 unmasks a novel electrocardiographic parameter that predicts initiation of torsade de pointes.
2002 Feb 12
Purinergic modulation of vascular sympathetic neurotransmission.
2002 Jan
Interaction of nitric oxide with calcium in the mesenteric bed of bile duct-ligated rats.
2002 Jan
Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles.
2002 Jul 30
Blood-brain barrier breakdown in septic encephalopathy and brain tumours.
2002 Jun
Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors.
2002 Mar
Modulation of Na-K-2Cl cotransport by intracellular Cl(-) and protein kinase C-delta in Calu-3 cells.
2002 May
Acute vascular effects of the selective estrogen receptor modulator EM-652 (SCH 57068) in the rat mesenteric vascular bed.
2003 Feb
The effects of volatile anesthetics on nonadrenergic, noncholinergic depressor responses in rats.
2003 Jan
Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers.
2003 Jan
Vasoconstrictor responsiveness of tail arteries from endotoxaemic rats.
2003 Jan 24
Hormonal influence on expression and functionality of alpha1-adrenoceptor in rat submandibular gland.
2003 Jan 31
L-Erythro-methoxamine is more potent than phenylephrine in effecting contraction of internal anal sphincter in vitro.
2003 Jul
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
Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers.
2003 Oct
Fish Balistes capriscus skin extract-induced relaxation in mesenteric arterial bed of rat.
2003 Oct
Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis.
2003 Oct 6
Influence of caveolin on constitutively activated recombinant eNOS: insights into eNOS dysfunction in BDL rat liver.
2003 Sep
Novel form of long-term synaptic depression in rat hippocampus induced by activation of alpha 1 adrenergic receptors.
2004 Feb
Patents

Sample Use Guides

Patients suffering fecal incontinence were administered 10 mg of Methoxamine as a slow release suppository into the anal canal.
Route of Administration: Rectal
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
INN   MI   VANDF   WHO-DD  
INN  
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
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
NCI_THESAURUS C29709
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
WHO-VATC QC01CA10
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
Code System Code Type Description
WIKIPEDIA
METHOXAMINE
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
ChEMBL
CHEMBL524
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
CAS
390-28-3
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
FDA UNII
HUQ1KC1YLI
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
RXCUI
6853
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY RxNorm
MERCK INDEX
M7328
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY Merck Index
PUBCHEM
688523
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
INN
209
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
DRUG CENTRAL
1753
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
IUPHAR
483
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
CHEBI
6839
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
EVMPD
SUB08857MIG
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
EPA CompTox
DTXSID0023290
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
ECHA (EC/EINECS)
206-867-3
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
NCI_THESAURUS
C66119
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
MESH
D008729
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
DRUG BANK
DB00723
Created by admin on Fri Dec 16 20:23:28 UTC 2022 , Edited by admin on Fri Dec 16 20:23:28 UTC 2022
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> AGONIST
Related Record Type Details
ACTIVE MOIETY