Identification

Name
Metocurine
Accession Number
DB01336
Type
Small Molecule
Groups
Approved
Description

Dimethyltubocurarinium (INN) or metocurine (USAN), also known as dimethyltubocurarine, is a non-depolarizing muscle relaxant. Patients on chronic anticonvulsant drugs are relatively resistant to metocurine. [1]

Structure
Thumb
Synonyms
  • Dimethylchondrocurarine
  • O,O-Dimethylchondrocurarine
External IDs
BRN 3583380
Product Ingredients
IngredientUNIICASInChI Key
Metocurine chloride15BE4G33H233335-58-9IRPSJVWFSWAZSZ-OIUSMDOTSA-L
Categories
UNII
V0M92G2U26
CAS number
5152-30-7
Weight
Average: 652.8189
Monoisotopic: 652.351237278
Chemical Formula
C40H48N2O6
InChI Key
JFXBEKISTKFVAB-AJQTZOPKSA-N
InChI
InChI=1S/C40H48N2O6/c1-41(2)17-15-27-22-34(44-6)36-24-30(27)31(41)19-25-9-12-29(13-10-25)47-40-38-28(23-37(45-7)39(40)46-8)16-18-42(3,4)32(38)20-26-11-14-33(43-5)35(21-26)48-36/h9-14,21-24,31-32H,15-20H2,1-8H3/q+2/t31-,32+/m0/s1
IUPAC Name
(1S,16R)-9,10,21,25-tetramethoxy-15,15,30,30-tetramethyl-7,23-dioxa-15,30-diazaheptacyclo[22.6.2.2^{3,6}.1^{8,12}.1^{18,22}.0^{27,31}.0^{16,34}]hexatriaconta-3,5,8(34),9,11,18(33),19,21,24,26,31,35-dodecaene-15,30-diium
SMILES
[H][[email protected]@]12CC3=CC=C(OC4=C5C(CC[N+](C)(C)[[email protected]]5([H])CC5=CC(OC6=C(OC)C=C(CC[N+]1(C)C)C2=C6)=C(OC)C=C5)=CC(OC)=C4OC)C=C3

Pharmacology

Indication

Metocurine is a muscle relaxant.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Metocurine antagonizes the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. This antagonism is inhibited, and neuromuscular block reversed, by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinMetocurine may increase the arrhythmogenic activities of Acetyldigitoxin.Approved
AcetyldigoxinMetocurine may increase the arrhythmogenic activities of Acetyldigoxin.Experimental
AclarubicinAclarubicin may increase the respiratory depressant activities of Metocurine.Investigational
AldoxorubicinAldoxorubicin may increase the respiratory depressant activities of Metocurine.Investigational
AmikacinAmikacin may increase the respiratory depressant activities of Metocurine.Approved, Vet Approved
AmrubicinAmrubicin may increase the respiratory depressant activities of Metocurine.Approved, Investigational
AnnamycinAnnamycin may increase the respiratory depressant activities of Metocurine.Investigational
ApramycinApramycin may increase the respiratory depressant activities of Metocurine.Experimental, Vet Approved
ArbekacinArbekacin may increase the respiratory depressant activities of Metocurine.Approved, Investigational
BekanamycinBekanamycin may increase the respiratory depressant activities of Metocurine.Experimental
Botulinum Toxin Type ABotulinum Toxin Type A may increase the neuromuscular blocking activities of Metocurine.Approved, Investigational
Botulinum Toxin Type BMetocurine may increase the neuromuscular blocking activities of Botulinum Toxin Type B.Approved
BumetanideBumetanide may decrease the neuromuscular blocking activities of Metocurine.Approved
CapreomycinCapreomycin may increase the neuromuscular blocking activities of Metocurine.Approved
ChlortetracyclineChlortetracycline may increase the neuromuscular blocking activities of Metocurine.Approved, Investigational, Vet Approved
ClindamycinClindamycin may increase the neuromuscular blocking activities of Metocurine.Approved, Vet Approved
ColistimethateColistimethate may increase the neuromuscular blocking activities of Metocurine.Approved, Vet Approved
CyclosporineCyclosporine may increase the neuromuscular blocking activities of Metocurine.Approved, Investigational, Vet Approved
CymarinMetocurine may increase the arrhythmogenic activities of Cymarin.Experimental
DaunorubicinDaunorubicin may increase the respiratory depressant activities of Metocurine.Approved
DemeclocyclineDemeclocycline may increase the neuromuscular blocking activities of Metocurine.Approved
DeslanosideMetocurine may increase the arrhythmogenic activities of Deslanoside.Approved
DibekacinDibekacin may increase the respiratory depressant activities of Metocurine.Experimental
DigitoxinMetocurine may increase the arrhythmogenic activities of Digitoxin.Approved, Investigational
DigoxinMetocurine may increase the arrhythmogenic activities of Digoxin.Approved
Digoxin Immune Fab (Ovine)Metocurine may increase the arrhythmogenic activities of Digoxin Immune Fab (Ovine).Approved
DihydrostreptomycinDihydrostreptomycin may increase the respiratory depressant activities of Metocurine.Investigational, Vet Approved
DoxorubicinDoxorubicin may increase the respiratory depressant activities of Metocurine.Approved, Investigational
DoxycyclineDoxycycline may increase the neuromuscular blocking activities of Metocurine.Approved, Investigational, Vet Approved
EpirubicinEpirubicin may increase the respiratory depressant activities of Metocurine.Approved
Etacrynic acidEtacrynic acid may decrease the neuromuscular blocking activities of Metocurine.Approved
FramycetinFramycetin may increase the respiratory depressant activities of Metocurine.Approved
FurosemideFurosemide may decrease the neuromuscular blocking activities of Metocurine.Approved, Vet Approved
GeneticinGeneticin may increase the respiratory depressant activities of Metocurine.Experimental
GentamicinGentamicin may increase the respiratory depressant activities of Metocurine.Approved, Vet Approved
GENTAMICIN C1AGENTAMICIN C1A may increase the respiratory depressant activities of Metocurine.Experimental
GitoformateMetocurine may increase the arrhythmogenic activities of Gitoformate.Experimental
GPX-150GPX-150 may increase the respiratory depressant activities of Metocurine.Investigational
Hygromycin BHygromycin B may increase the respiratory depressant activities of Metocurine.Vet Approved
IdarubicinIdarubicin may increase the respiratory depressant activities of Metocurine.Approved
IsepamicinIsepamicin may increase the respiratory depressant activities of Metocurine.Experimental
KanamycinKanamycin may increase the respiratory depressant activities of Metocurine.Approved, Investigational, Vet Approved
Lanatoside CMetocurine may increase the arrhythmogenic activities of Lanatoside C.Experimental
LincomycinLincomycin may increase the neuromuscular blocking activities of Metocurine.Approved, Vet Approved
LithiumLithium may increase the neuromuscular blocking activities of Metocurine.Approved
LorpiprazoleThe therapeutic efficacy of Metocurine can be increased when used in combination with Lorpiprazole.Approved
MetildigoxinMetocurine may increase the arrhythmogenic activities of Metildigoxin.Experimental
MetrizamideMetrizamide may increase the respiratory depressant activities of Metocurine.Approved
MicronomicinMicronomicin may increase the respiratory depressant activities of Metocurine.Experimental
MinocyclineMinocycline may increase the neuromuscular blocking activities of Metocurine.Approved, Investigational
NeamineNeamine may increase the respiratory depressant activities of Metocurine.Experimental
NeomycinNeomycin may increase the respiratory depressant activities of Metocurine.Approved, Vet Approved
NetilmicinNetilmicin may increase the respiratory depressant activities of Metocurine.Approved, Investigational
OleandrinMetocurine may increase the arrhythmogenic activities of Oleandrin.Experimental, Investigational
OuabainMetocurine may increase the arrhythmogenic activities of Ouabain.Approved
ParomomycinParomomycin may increase the respiratory depressant activities of Metocurine.Approved, Investigational
PeruvosideMetocurine may increase the arrhythmogenic activities of Peruvoside.Experimental
PirarubicinPirarubicin may increase the respiratory depressant activities of Metocurine.Investigational
PiretanidePiretanide may decrease the neuromuscular blocking activities of Metocurine.Experimental
PirlimycinPirlimycin may increase the neuromuscular blocking activities of Metocurine.Vet Approved
PlazomicinPlazomicin may increase the respiratory depressant activities of Metocurine.Investigational
PlicamycinPlicamycin may increase the respiratory depressant activities of Metocurine.Approved, Investigational, Withdrawn
Polymyxin B SulfatePolymyxin B Sulfate may increase the neuromuscular blocking activities of Metocurine.Approved, Vet Approved
ProcainamideProcainamide may increase the neuromuscular blocking activities of Metocurine.Approved
ProscillaridinMetocurine may increase the arrhythmogenic activities of Proscillaridin.Experimental
PuromycinPuromycin may increase the respiratory depressant activities of Metocurine.Experimental
QuinidineQuinidine may increase the neuromuscular blocking activities of Metocurine.Approved
QuinineQuinine may increase the neuromuscular blocking activities of Metocurine.Approved
RibostamycinRibostamycin may increase the respiratory depressant activities of Metocurine.Approved, Investigational
SabarubicinSabarubicin may increase the respiratory depressant activities of Metocurine.Investigational
SisomicinSisomicin may increase the respiratory depressant activities of Metocurine.Investigational
SP1049CSP1049C may increase the respiratory depressant activities of Metocurine.Investigational
SpectinomycinSpectinomycin may increase the respiratory depressant activities of Metocurine.Approved, Investigational, Vet Approved
StreptomycinStreptomycin may increase the respiratory depressant activities of Metocurine.Approved, Vet Approved
StreptozocinStreptozocin may increase the respiratory depressant activities of Metocurine.Approved
TobramycinTobramycin may increase the respiratory depressant activities of Metocurine.Approved, Investigational
TorasemideTorasemide may decrease the neuromuscular blocking activities of Metocurine.Approved
ValrubicinValrubicin may increase the respiratory depressant activities of Metocurine.Approved
VancomycinVancomycin may increase the neuromuscular blocking activities of Metocurine.Approved
Zoptarelin doxorubicinZoptarelin doxorubicin may increase the respiratory depressant activities of Metocurine.Investigational
ZorubicinZorubicin may increase the respiratory depressant activities of Metocurine.Experimental
Food Interactions
Not Available

References

General References
  1. Spacek A, Neiger FX, Krenn CG, Hoerauf K, Kress HG: Rocuronium-induced neuromuscular block is affected by chronic carbamazepine therapy. Anesthesiology. 1999 Jan;90(1):109-12. [PubMed:9915319]
External Links
Human Metabolome Database
HMDB0015429
KEGG Compound
C07919
PubChem Compound
21233
PubChem Substance
46508044
ChemSpider
19961
BindingDB
50094708
ChEBI
6900
ChEMBL
CHEMBL1259
Therapeutic Targets Database
DAP000352
PharmGKB
PA164749507
HET
CU9
Wikipedia
Dimethyltubocurarinium
PDB Entries
3peo

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility6.42e-06 mg/mLALOGPS
logP2.36ALOGPS
logP-1.8ChemAxon
logS-8ALOGPS
pKa (Strongest Acidic)12.99ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area55.38 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity211.94 m3·mol-1ChemAxon
Polarizability73.08 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.871
Blood Brain Barrier+0.9597
Caco-2 permeable+0.7462
P-glycoprotein substrateSubstrate0.8469
P-glycoprotein inhibitor INon-inhibitor0.6124
P-glycoprotein inhibitor IINon-inhibitor0.82
Renal organic cation transporterNon-inhibitor0.533
CYP450 2C9 substrateNon-substrate0.8465
CYP450 2D6 substrateNon-substrate0.5836
CYP450 3A4 substrateSubstrate0.6987
CYP450 1A2 substrateNon-inhibitor0.9391
CYP450 2C9 inhibitorNon-inhibitor0.9626
CYP450 2D6 inhibitorNon-inhibitor0.908
CYP450 2C19 inhibitorNon-inhibitor0.9468
CYP450 3A4 inhibitorNon-inhibitor0.8976
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.976
Ames testAMES toxic0.6059
CarcinogenicityNon-carcinogens0.9074
BiodegradationNot ready biodegradable0.8898
Rat acute toxicity2.7086 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8306
hERG inhibition (predictor II)Non-inhibitor0.6067
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Tetrahydroisoquinolines / Anisoles / Aralkylamines / Alkyl aryl ethers / Tetraalkylammonium salts / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organic salts / Hydrocarbon derivatives
show 1 more
Substituents
Diaryl ether / Tetrahydroisoquinoline / Anisole / Alkyl aryl ether / Aralkylamine / Benzenoid / Quaternary ammonium salt / Tetraalkylammonium salt / Oxacycle / Organoheterocyclic compound
show 9 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
isoquinolines (CHEBI:6900)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Drug binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA2
Uniprot ID
Q15822
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight
59764.82 Da
References
  1. Liu M, Dilger JP: Synergy between pairs of competitive antagonists at adult human muscle acetylcholine receptors. Anesth Analg. 2008 Aug;107(2):525-33. doi: 10.1213/ane.0b013e31817b4469. [PubMed:18633030]
  2. Liu M, Dilger JP: Site selectivity of competitive antagonists for the mouse adult muscle nicotinic acetylcholine receptor. Mol Pharmacol. 2009 Jan;75(1):166-73. doi: 10.1124/mol.108.051060. Epub 2008 Oct 8. [PubMed:18842832]
  3. Groebe DR, Dumm JM, Abramson SN: Irreversible inhibition of nicotinic acetylcholine receptors by the bipinnatins. Toxin activation and kinetics of receptor inhibition. J Biol Chem. 1994 Mar 25;269(12):8885-91. [PubMed:8132625]
  4. Wang HL, Gao F, Bren N, Sine SM: Curariform antagonists bind in different orientations to the nicotinic receptor ligand binding domain. J Biol Chem. 2003 Aug 22;278(34):32284-91. Epub 2003 Jun 10. [PubMed:12799358]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Son SL, Waud DR: Effects of non-depolarizing neuromuscular blocking agents on the cardiac vagus nerve in the guineapig. Br J Anaesth. 1980 Oct;52(10):981-7. [PubMed:7437219]

Drug created on June 30, 2007 12:07 / Updated on January 19, 2018 10:55