Identification

Name
Methoxamine
Accession Number
DB00723  (APRD00062)
Type
Small Molecule
Groups
Approved, Investigational
Description

An alpha-adrenergic agonist that causes prolonged peripheral vasoconstriction. It has little if any direct effect on the central nervous system. [PubChem]

Structure
Thumb
Synonyms
  • Méthoxamédrine
  • Methoxamin
  • Méthoxamine
  • Methoxaminum
  • Metossamina
  • Metoxamina
  • Pseudomethoxamine
External IDs
NRL-001 / NRL001
Product Ingredients
IngredientUNIICASInChI Key
Methoxamine Hydrochloride8MB4MJ9R7L61-16-5YGRFXPCHZBRUKP-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vasoxyl Inj 20mg/mlLiquid20 mgIntramuscular; IntravenousGlaxo Wellcome1950-12-312001-01-25Canada
International/Other Brands
Mexan (Nippon Shinyaku) / Vasoxine / Vasoxyl
Categories
UNII
HUQ1KC1YLI
CAS number
390-28-3
Weight
Average: 211.2576
Monoisotopic: 211.120843415
Chemical Formula
C11H17NO3
InChI Key
WJAJPNHVVFWKKL-UHFFFAOYSA-N
InChI
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
IUPAC Name
2-amino-1-(2,5-dimethoxyphenyl)propan-1-ol
SMILES
COC1=CC(C(O)C(C)N)=C(OC)C=C1

Pharmacology

Indication

Indicated for the treatment and management of hypotension.

Pharmacodynamics

Methoxamine is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. Methoxamine is indicated for prevention and treatment of the acute hypotensive state occurring with spinal anesthesia. It is also indicated as adjunctive treatment of hypotension due to hemorrhage, reactions to medications, surgical complications, and shock associated with brain damage due to trauma or tumor. Methoxamine acts on both α1-adrenergic receptors but appears to have no effect on β-adrenergic receptors. It acts by increasing the force of the heart's pumping action as well as constricting peripheral blood vessels.

Mechanism of action

Methoxamine acts through peripheral vasoconstriction by acting as a pure alpha-1 adrenergic receptor agonist, consequently increasing systemic blood pressure (both systolic and diastolic).

TargetActionsOrganism
AAlpha-1A adrenergic receptor
agonist
Human
UAlpha-1B adrenergic receptor
agonist
Human
UAlpha-1D adrenergic receptor
binder
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Low

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
6-O-benzylguanineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 6-O-benzylguanine.
7-DeazaguanineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 7-Deazaguanine.
7,9-DimethylguanineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 7,9-Dimethylguanine.
8-azaguanineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 8-azaguanine.
8-chlorotheophyllineThe risk or severity of adverse effects can be increased when Methoxamine is combined with 8-chlorotheophylline.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014861
KEGG Drug
D08201
KEGG Compound
C07513
PubChem Compound
6082
PubChem Substance
46506264
ChemSpider
5857
BindingDB
50026777
ChEBI
6839
ChEMBL
CHEMBL524
Therapeutic Targets Database
DAP000796
PharmGKB
PA450431
IUPHAR
483
Guide to Pharmacology
GtP Drug Page
Wikipedia
Methoxamine
ATC Codes
C01CA10 — Methoxamine
MSDS
Download (24.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentIncontinence1
1CompletedTreatmentIncontinence, Fecal6
2CompletedTreatmentIncontinence, Fecal1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntramuscular; Intravenous20 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble (185 g/L)Not Available
logP0.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility9.21 mg/mLALOGPS
logP0.41ALOGPS
logP0.57ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)13.61ChemAxon
pKa (Strongest Basic)9.28ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area64.71 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity57.84 m3·mol-1ChemAxon
Polarizability22.79 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9751
Blood Brain Barrier-0.8857
Caco-2 permeable+0.5637
P-glycoprotein substrateNon-substrate0.6457
P-glycoprotein inhibitor INon-inhibitor0.9698
P-glycoprotein inhibitor IINon-inhibitor0.9823
Renal organic cation transporterNon-inhibitor0.9217
CYP450 2C9 substrateNon-substrate0.8341
CYP450 2D6 substrateNon-substrate0.6858
CYP450 3A4 substrateNon-substrate0.6635
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9506
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8328
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8476
Ames testNon AMES toxic0.637
CarcinogenicityNon-carcinogens0.8754
BiodegradationNot ready biodegradable0.9117
Rat acute toxicity2.0534 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.951
hERG inhibition (predictor II)Non-inhibitor0.9331
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-014i-0900000000-c18e80e68507135a55de
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-000f-1980000000-5a3cb42851d6378d998c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03dl-0690000000-5602a5d1ca570bcf9aa6
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-0900000000-1b92cefe5d27ce45aad1
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03dj-0900000000-bd56a39cbf83b4b15579
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03kj-1900000000-4dc22029f0246da362e5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01bd-4900000000-5bd9da97330739f95161
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0006-0900000000-89ab0b5f7f3887939aea

Taxonomy

Description
This compound belongs to the class of organic compounds known as dimethoxybenzenes. These are organic aromatic compounds containing a monocyclic benzene moiety carrying exactly two methoxy groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Methoxybenzenes
Direct Parent
Dimethoxybenzenes
Alternative Parents
Phenylpropanes / Phenoxy compounds / Anisoles / Aralkylamines / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives
show 1 more
Substituents
Dimethoxybenzene / P-dimethoxybenzene / Phenylpropane / Anisole / Phenol ether / Phenoxy compound / Alkyl aryl ether / Aralkylamine / Secondary alcohol / 1,2-aminoalcohol
show 13 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
amphetamines (CHEBI:6839)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Satoh M, Kojima C, Kokubu N, Takayanagi I: Alpha 1-adrenoceptor subtypes mediating the regulation and modulation of Ca2+ sensitization in rabbit thoracic aorta. Eur J Pharmacol. 1994 Nov 24;265(3):133-9. [PubMed:7875228]
  2. Suzuki E, Tsujimoto G, Tamura K, Hashimoto K: Two pharmacologically distinct alpha 1-adrenoceptor subtypes in the contraction of rabbit aorta: each subtype couples with a different Ca2+ signalling mechanism and plays a different physiological role. Mol Pharmacol. 1990 Nov;38(5):725-36. [PubMed:1978244]
  3. Piascik MT, Sparks MS, Pruitt TA, Soltis EE: Evidence for a complex interaction between the subtypes of the alpha 1-adrenoceptor. Eur J Pharmacol. 1991 Jul 9;199(3):279-89. [PubMed:1680715]
  4. Sattar MA, Johns EJ: Evidence for an alpha 1-adrenoceptor subtype mediating adrenergic vasoconstriction in Wistar normotensive and stroke-prone spontaneously hypertensive rat kidney. J Cardiovasc Pharmacol. 1994 Feb;23(2):232-9. [PubMed:7511752]
  5. Hoang TV, Choe EU, Burgess RS, Cork RC, Flint LM, Ferrara JJ: Characterization of alpha-adrenoceptor activity in the preterm piglet mesentery. J Pediatr Surg. 1996 Dec;31(12):1659-62. [PubMed:8986981]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Tsujimoto G, Tsujimoto A, Suzuki E, Hashimoto K: Glycogen phosphorylase activation by two different alpha 1-adrenergic receptor subtypes: methoxamine selectively stimulates a putative alpha 1-adrenergic receptor subtype (alpha 1a) that couples with Ca2+ influx. Mol Pharmacol. 1989 Jul;36(1):166-76. [PubMed:2546049]
  2. Simpson P: Stimulation of hypertrophy of cultured neonatal rat heart cells through an alpha 1-adrenergic receptor and induction of beating through an alpha 1- and beta 1-adrenergic receptor interaction. Evidence for independent regulation of growth and beating. Circ Res. 1985 Jun;56(6):884-94. [PubMed:2988814]
  3. Oleksa LM, Hool LC, Harvey RD: Alpha 1-adrenergic inhibition of the beta-adrenergically activated Cl- current in guinea pig ventricular myocytes. Circ Res. 1996 Jun;78(6):1090-9. [PubMed:8635240]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. Waugh DJ, Gaivin RJ, Zuscik MJ, Gonzalez-Cabrera P, Ross SA, Yun J, Perez DM: Phe-308 and Phe-312 in transmembrane domain 7 are major sites of alpha 1-adrenergic receptor antagonist binding. Imidazoline agonists bind like antagonists. J Biol Chem. 2001 Jul 6;276(27):25366-71. Epub 2001 Apr 30. [PubMed:11331292]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Zeng A, Yuan B, Wang C, Yang G, He L: Frontal analysis of cell-membrane chromatography for determination of drug-alpha(1D) adrenergic receptor affinity. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jul 1;877(20-21):1833-7. doi: 10.1016/j.jchromb.2009.05.021. Epub 2009 May 18. [PubMed:19493707]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:44