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
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
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.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
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 |
4.86 null [pKi] | ||
Target ID: P25100 Gene ID: 146.0 Gene Symbol: ADRA1D Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19493707 |
1299.27 nM [Kd] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Vasoxyl Approved UseUnknown Launch Date3.78691191E11 |
Cmax
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 |
T1/2
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 |
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
AE | Significance | Dose | Population |
---|---|---|---|
Heart rate decreased | 8 patients DLT |
15 mg single, rectal Recommended |
healthy, 18 - 60 years n = 24 Health Status: healthy Age Group: 18 - 60 years Sex: M+F Population Size: 24 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
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
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00893607
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29196668
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
Edited
Fri Dec 16 20:23:28 UTC 2022
by
admin
on
Fri Dec 16 20:23:28 UTC 2022
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Record UNII |
HUQ1KC1YLI
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Record Status |
Validated (UNII)
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Record Version |
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WHO-ATC |
C01CA10
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NCI_THESAURUS |
C29709
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WHO-VATC |
QC01CA10
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METHOXAMINE
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CHEMBL524
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390-28-3
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HUQ1KC1YLI
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6853
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M7328
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688523
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209
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SUB08857MIG
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206-867-3
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C66119
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D008729
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DB00723
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT | |||
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TARGET -> AGONIST |
Related Record | Type | Details | ||
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ACTIVE MOIETY |