U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
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
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
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
Effect of high extracellular Ca(2+) levels in spontaneously hypertensive rat aorta.
2001 Dec 7
Noradrenaline stimulates 5-hydroxytryptamine release from mouse ileal tissues via alpha(2)-adrenoceptors.
2001 Dec 7
Assessment of the pro-arrhythmic potential of anti-arrhythmic drugs: an experimental approach.
2001 Jan
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
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
MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau.
2001 Nov
Abrogation of alpha-adrenergic vasoactivity in chronically inflamed rat knee joints.
2001 Sep
Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers.
2002 Aug
A mitogen-activated protein kinase is involved in the inotropic but not chronotropic actions of adrenoceptor agonists and endothelin-1.
2002 Aug
Pregnancy and acute baroreflex resetting in conscious rabbits.
2002 Aug
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
Male-female differences in the relative contribution of endothelial vasodilators released by rat tail artery.
2002 Aug 23
Mediation of contraction in rat cauda epididymidis by alpha-adrenoceptors.
2002 Dec
Dual adrenergic control of in vivo choline levels in the mouse major salivary glands.
2002 Feb
Existence of functional alpha1A- and alpha1D- but no alpha1B-adrenoceptor subtypes in rat common carotid arteries.
2002 Feb
Types of adrenoreceptors mediating responses of rabbit gastric muscularis mucosae.
2002 Feb
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
Activation of alpha 1-adrenoceptors is not essential for the mediation of ischaemic preconditioning in rat heart.
2002 Jan-Feb
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
Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension.
2002 Jun
Compression and expansion wavefront travel in canine ascending aortic flow: wave intensity analysis.
2002 Mar
Potential anaphylactic shock with abciximab readministration.
2002 Mar
Use of methoxamine in the resuscitation of epinephrine resistant electromechanical dissociation.
2002 Mar
Impairment of autoregulation following cortical venous occlusion in the rat.
2002 Mar
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
Mechanism underlying gamma-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats.
2002 Mar 1
Modulation of Na-K-2Cl cotransport by intracellular Cl(-) and protein kinase C-delta in Calu-3 cells.
2002 May
ANP potentiates nonarterial baroreflex bradycardia: evidence from sinoaortic denervation in rats.
2002 May 31
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
Effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in perfused rat mesenteric arterial beds.
2003
Deficit in nitric oxide production in cirrhotic rat livers is located in the sinusoidal and postsinusoidal areas.
2003 Apr
Evidence for the role of alpha1D- and alpha1A-adrenoceptors in contraction of the rat mesenteric artery.
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
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 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
  • 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 Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
NCI_THESAURUS C29709
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
WHO-VATC QC01CA10
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
Code System Code Type Description
WIKIPEDIA
METHOXAMINE
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
ChEMBL
CHEMBL524
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
CAS
390-28-3
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
FDA UNII
HUQ1KC1YLI
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
RXCUI
6853
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY RxNorm
MERCK INDEX
M7328
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY Merck Index
PUBCHEM
688523
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
SMS_ID
100000081455
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
INN
209
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
DRUG CENTRAL
1753
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
IUPHAR
483
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
CHEBI
6839
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
EVMPD
SUB08857MIG
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
EPA CompTox
DTXSID0023290
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
ECHA (EC/EINECS)
206-867-3
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
NCI_THESAURUS
C66119
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
MESH
D008729
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
DRUG BANK
DB00723
Created by admin on Wed Jul 05 23:56:56 UTC 2023 , Edited by admin on Wed Jul 05 23:56:56 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> AGONIST
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY