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][C@@]12CC3=CC=C(OC4=C5C(CC[N+](C)(C)[C@]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.

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
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Metocurine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Metocurine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Metocurine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Metocurine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Metocurine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Metocurine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Metocurine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Metocurine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcepromazineThe risk or severity of adverse effects can be increased when Metocurine is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Metocurine is combined with Aceprometazine.
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 November 02, 2018 09:09