Identification

Name
Metaraminol
Accession Number
DB00610  (APRD00555)
Type
Small Molecule
Groups
Approved, Investigational
Description

An adrenergic agonist that acts predominantly at alpha adrenergic receptors and also stimulates the release of norepinephrine. It has been used primarily as a vasoconstrictor in the treatment of hypotension. [PubChem]

Structure
Thumb
Synonyms
  • (-)-Erythro-metaraminol
  • 1-(m-Hydroxyphenyl)-2-amino-1-propanol
  • 1-Metaraminol
  • 2-Amino-1-(m-hydroxyphenyl)-1-propanol
  • 3-Hydroxyphenylisopropanolamine
  • alpha-(1-Aminoethyl)-3-hydroxybenzenemethanol
  • alpha-(m-Hydroxyphenyl)-beta-aminopropanol
  • Hydroxynorephedrine
  • L-Metaraminol
  • m-Hydroxy norephedrine
  • m-Hydroxyphenylpropanolamine
  • m-Hydroxypropadrine
  • Metaraminol
  • Métaraminol
  • Metaraminolum
Product Ingredients
IngredientUNIICASInChI Key
Metaraminol BitartrateZC4202M9P333402-03-8VENXSELNXQXCNT-IJYXXVHRSA-N
Metaraminol TartrateNot AvailableNot AvailableNot applicable
International/Other Brands
Aramine (Merck) / Metaramin / Pressonex
Categories
UNII
818U2PZ2EH
CAS number
54-49-9
Weight
Average: 167.205
Monoisotopic: 167.094628665
Chemical Formula
C9H13NO2
InChI Key
WXFIGDLSSYIKKV-RCOVLWMOSA-N
InChI
InChI=1S/C9H13NO2/c1-6(10)9(12)7-3-2-4-8(11)5-7/h2-6,9,11-12H,10H2,1H3/t6-,9-/m0/s1
IUPAC Name
3-[(1R,2S)-2-amino-1-hydroxypropyl]phenol
SMILES
C[C@H](N)[C@H](O)C1=CC(O)=CC=C1

Pharmacology

Indication

For the treatment and prevention of hypotension due to hemorrhage, spinal anesthesia, and shock associated with brain damage

Pharmacodynamics

Metaraminol is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. Metaraminol 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. Metaraminol 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

Metaraminol acts through peripheral vasoconstriction by acting as a pure alpha-1 adrenergic receptor agonist, consequently increasing systemic blood pressure (both systolic & diastolic). Its effect is thought to be associated with the inhibition of adenyl cyclase which leads to an inhibition of the production of cAMP. Another effect of Metaraminol is that it releases norepinephrine from its storage sites indirectly.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
agonist
Human
Absorption

The effect starts 1-2 min after IV injection, 10 min after IM injection, 5-20 min after subcutaneous injection.

Volume of distribution
Not Available
Protein binding

Approximately 45%

Metabolism

Hepatic

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

LD50=240 mg/kg (rat, oral); LD50=99 mg/kg (mouse, oral)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypertensive activities of Metaraminol.
AcebutololThe therapeutic efficacy of Metaraminol can be decreased when used in combination with Acebutolol.
AcepromazineAcepromazine may decrease the vasoconstricting activities of Metaraminol.
AlfuzosinThe therapeutic efficacy of Metaraminol can be decreased when used in combination with Alfuzosin.
AmineptineAmineptine may increase the vasopressor activities of Metaraminol.
AmitriptylineAmitriptyline may increase the vasopressor activities of Metaraminol.
AmitriptylinoxideAmitriptylinoxide may increase the vasopressor activities of Metaraminol.
AmoxapineAmoxapine may increase the vasopressor activities of Metaraminol.
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Metaraminol.
AripiprazoleAripiprazole may decrease the vasoconstricting activities of Metaraminol.
Food Interactions
Not Available

References

General References
  1. McDonald M, Santucci RA: Successful management of stuttering priapism using home self-injections of the alpha-agonist metaraminol. Int Braz J Urol. 2004 Mar-Apr;30(2):121-2. [PubMed:15703094]
  2. Koga S, Shiraishi K, Saito Y: Post-traumatic priapism treated with metaraminol bitartrate: case report. J Trauma. 1990 Dec;30(12):1591-3. [PubMed:2258979]
  3. Block T, Sturm W, Ernst G, Staehler G, Schmiedt E: [Metaraminol in therapy of various forms of priapism]. Urologe A. 1988 Jul;27(4):225-9. [PubMed:3140463]
External Links
Human Metabolome Database
HMDB0014748
KEGG Compound
C07146
PubChem Compound
5906
PubChem Substance
46505593
ChemSpider
5695
ChEBI
6794
ChEMBL
CHEMBL1201319
Therapeutic Targets Database
DAP000225
PharmGKB
PA164748761
RxList
RxList Drug Page
Wikipedia
Metaraminol
ATC Codes
C01CA09 — Metaraminol
MSDS
Download (52.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentArterial Hypotension1
3WithdrawnTreatmentPreeclampsia / Pregnancy Toxemias1
Not AvailableUnknown StatusDiagnosticPreeclampsia1

Pharmacoeconomics

Manufacturers
  • Merck and co inc
  • Abraxis pharmaceutical products
  • App pharmaceuticals llc
  • Elkins sinn div ah robins co inc
  • Gd searle llc
Packagers
  • Physicians Total Care Inc.
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)107.5 °CPhysProp
boiling point (°C)218 °CPhysProp
water solubility1000 g/LNot Available
logP-0.27HANSCH,C ET AL. (1995); ion-corrected
pKa8.79SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility12.8 mg/mLALOGPS
logP-0.59ALOGPS
logP-0.045ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)9.03ChemAxon
pKa (Strongest Basic)9.68ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area66.48 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity46.89 m3·mol-1ChemAxon
Polarizability17.84 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9922
Blood Brain Barrier-0.8926
Caco-2 permeable+0.6112
P-glycoprotein substrateNon-substrate0.721
P-glycoprotein inhibitor INon-inhibitor0.9907
P-glycoprotein inhibitor IINon-inhibitor0.9961
Renal organic cation transporterNon-inhibitor0.9152
CYP450 2C9 substrateNon-substrate0.7922
CYP450 2D6 substrateNon-substrate0.6311
CYP450 3A4 substrateNon-substrate0.7459
CYP450 1A2 substrateNon-inhibitor0.899
CYP450 2C9 inhibitorNon-inhibitor0.9538
CYP450 2D6 inhibitorNon-inhibitor0.9724
CYP450 2C19 inhibitorNon-inhibitor0.9255
CYP450 3A4 inhibitorNon-inhibitor0.8264
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9205
Ames testNon AMES toxic0.8102
CarcinogenicityNon-carcinogens0.837
BiodegradationNot ready biodegradable0.6456
Rat acute toxicity2.7863 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9126
hERG inhibition (predictor II)Non-inhibitor0.9492
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
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/MSsplash10-0uxr-0900000000-54fdef7fb806e9618517
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-1900000000-53aa60f30061472008e2
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-3900000000-03da43641cb5f6da239a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-056r-9700000000-bb18dd53ad6ac9a58e4f
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004i-9300000000-3d3ebdc9e7c553d5122c

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylpropanes
Direct Parent
Phenylpropanes
Alternative Parents
Aralkylamines / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Secondary alcohols / 1,2-aminoalcohols / Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Phenylpropane / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Aralkylamine / 1,2-aminoalcohol / Secondary alcohol / Organic nitrogen compound / Aromatic alcohol / Hydrocarbon derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
phenylethanolamines (CHEBI:6794)

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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Tatsuta M, Iishi H, Baba M, Yano H, Sakai N, Uehara H, Hirasawa R, Nakaizumi A: Alpha1-adrenoceptor stimulation enhances experimental gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Int J Cancer. 1998 Jul 29;77(3):467-9. [PubMed:9663612]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:47