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Identification
NameMethoxamine
Accession NumberDB00723  (APRD00062)
Typesmall molecule
Groupsapproved
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
SynonymLanguageCode
MéthoxamédrineNot AvailableIS
MethoxaminGermanINN
MéthoxamineFrenchINN
MethoxaminumLatinINN
MetossaminaNot AvailableDCIT
MetoxaminaSpanishINN
PseudomethoxamineNot AvailableNot Available
SID90341132Not AvailableNot Available
VasoxylNot AvailableNot Available
Salts
Name/CAS Structure Properties
Methoxamine Hydrochloride
Thumb Not applicable DBSALT000971
Brand names
NameCompany
MexanNippon Shinyaku
VasoxineNot Available
VasoxylNot Available
Brand mixturesNot Available
Categories
CAS number390-28-3
WeightAverage: 211.2576
Monoisotopic: 211.120843415
Chemical FormulaC11H17NO3
InChI KeyWJAJPNHVVFWKKL-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenethylamines
Direct parentAmphetamines and Derivatives
Alternative parentsAnisoles; Alkyl Aryl Ethers; Secondary Alcohols; 1,2-Aminoalcohols; Polyamines; Monoalkylamines
Substituentsphenol ether; anisole; alkyl aryl ether; 1,2-aminoalcohol; secondary alcohol; ether; polyamine; amine; primary amine; primary aliphatic amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Pharmacology
IndicationIndicated for the treatment and management of hypotension.
PharmacodynamicsMethoxamine 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 actionMethoxamine acts through peripheral vasoconstriction by acting as a pure alpha-1 adrenergic receptor agonist, consequently increasing systemic blood pressure (both systolic and diastolic).
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingLow
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9751
Blood Brain Barrier - 0.8857
Caco-2 permeable + 0.5637
P-glycoprotein substrate Non-substrate 0.6457
P-glycoprotein inhibitor I Non-inhibitor 0.9698
P-glycoprotein inhibitor II Non-inhibitor 0.9823
Renal organic cation transporter Non-inhibitor 0.9217
CYP450 2C9 substrate Non-substrate 0.8341
CYP450 2D6 substrate Non-substrate 0.6858
CYP450 3A4 substrate Non-substrate 0.6635
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9506
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.8328
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8476
Ames test Non AMES toxic 0.637
Carcinogenicity Non-carcinogens 0.8754
Biodegradation Not ready biodegradable 0.9117
Rat acute toxicity 2.0534 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.951
hERG inhibition (predictor II) Non-inhibitor 0.9331
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilitySoluble (185 g/L)Not Available
logP0.8Not Available
Predicted Properties
PropertyValueSource
water solubility9.21e+00 g/lALOGPS
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 area64.71ChemAxon
rotatable bond count4ChemAxon
refractivity57.84ChemAxon
polarizability22.79ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07513
PubChem Compound6082
PubChem Substance46506264
ChemSpider5857
BindingDB50026777
Therapeutic Targets DatabaseDAP000796
PharmGKBPA450431
IUPHAR483
Guide to Pharmacology483
Drug Product Database4480
WikipediaMethoxamine
ATC CodesC01CA10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(24.5 KB)
Interactions
Drug Interactions
Drug
AmitriptylineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of methoxamine.
AmoxapineThe tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of methoxamine.
ClomipramineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of methoxamine.
DesipramineThe tricyclic antidepressant, desipramine, increases the sympathomimetic effect of methoxamine.
DoxepinThe tricyclic antidepressant, doxepin, increases the sympathomimetic effect of methoxamine.
GuanethidineMethoxamine may decrease the effect of guanethidine.
ImipramineThe tricyclic antidepressant, imipramine, increases the sympathomimetic effect of methoxamine.
IsocarboxazidIncreased arterial pressure
LinezolidPossible increase of arterial pressure
MethyldopaIncreased arterial pressure
MidodrineIncreased arterial pressure
MoclobemideMoclobemide increases the sympathomimetic effect of methoxamine.
NortriptylineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of methoxamine.
PhenelzineIncreased arterial pressure
RasagilineIncreased arterial pressure
ReserpineIncreased arterial pressure
TranylcypromineThe MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha1-agonist, Methoxamine. Concomitant therapy should be avoided.
TrimipramineTrimipramine may increase the vasopressor effect of the alpha1-agonist, Methoxamine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
Food InteractionsNot Available

Targets

1. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

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
  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
  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
  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
  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

2. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 Details

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
  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
  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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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

3. Alpha-1D adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Alpha-1D adrenergic receptor P25100 Details

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

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Drug created on June 13, 2005 07:24 / Updated on January 08, 2014 09:32