Identification

Name
Metocurine Iodide
Accession Number
DB00416  (APRD01318)
Type
Small Molecule
Groups
Withdrawn
Description

Metocurine iodide is a benzylisoquinolinium competitive nondepolarizing neuromuscular blocking agent. It is used as an anesthesia adjunct to induce skeletal muscle relaxation and to reduce the intensity of muscle contractions in convulsive therapy Metocurine iodide has a moderate risk of inducing histamine release and has some ganglion blocking activity. Metocurine iodide can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. Metocurine Iodide is no longer available on the US market.

Structure
Thumb
Synonyms
  • (+)-O,O'-Dimethylchondrocurarine Di-iodide
  • Dimethyl Tubocurarine Iodide
  • Dimethyltubocurarine Iodide
  • Dimethyltubocurarinium iodide
  • Dimetiltubocurarinio, ioduro de
  • Metocurine iodide
  • Metocurini Iodidum
  • Metokuriinijodidi
  • Metokurinjodid
  • Trimethyltubocurarine Iodide
External IDs
NSC-36388
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Metubine Iodide Inj 2mg/mlLiquid2 mgIntravenousEli Lilly & Co. Ltd.1948-12-311998-08-04Canada
International/Other Brands
Metubine iodide
Categories
UNII
O0U0E87X7F
CAS number
7601-55-0
Weight
Average: 906.6279
Monoisotopic: 906.160174118
Chemical Formula
C40H48I2N2O6
InChI Key
DIGFQJFCDPKEPF-OIUSMDOTSA-L
InChI
InChI=1S/C40H48N2O6.2HI/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;2*1H/q+2;;/p-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[22.6.2.2³,⁶.1⁸,¹².1¹⁸,²².0²⁷,³¹.0¹⁶,³⁴]hexatriaconta-3,5,8(34),9,11,18(33),19,21,24,26,31,35-dodecaene-15,30-diium diiodide
SMILES
[I-].[I-].[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

For use as an anesthesia adjunct to induce skeletal muscle relaxation and to reduce the intensity of muscle contractions in convulsive therapy.

Structured Indications
Not Available
Pharmacodynamics

Metocurine iodide is a benzylisoquinolinium competitive nondepolarizing neuromuscular blocking agent. Metocurine iodide has a moderate risk of inducing histamine release and has some ganglion blocking activity. Metocurine iodide can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. As with other nondepolarizing neuromuscular blockers, the time to onset of paralysis decreases and the duration of maximum effect increases with increasing doses of metocurine iodide. Repeated administration of maintenance doses of metocurine iodide has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeat doses does not change with additional doses. Repeat doses can therefore be administered at relatively regular intervals with predictable results.

Mechanism of action

Metocurine iodide 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
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

35% in plasma

Metabolism
Not Available
Route of elimination
Not Available
Half life

3 to 4 hours

Clearance
Not Available
Toxicity

Excessive doses can be expected to produce enhanced pharmacological effects. Overdosage may increase the risk of histamine release and cardiovascular effects, especially hypotension.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinMetocurine Iodide may increase the arrhythmogenic activities of Acetyldigitoxin.Approved
AcetyldigoxinMetocurine Iodide may increase the arrhythmogenic activities of Acetyldigoxin.Experimental
AclarubicinAclarubicin may increase the respiratory depressant activities of Metocurine Iodide.Investigational
AmikacinAmikacin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Vet Approved
AmrubicinAmrubicin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational
annamycinannamycin may increase the respiratory depressant activities of Metocurine Iodide.Investigational
ApramycinApramycin may increase the respiratory depressant activities of Metocurine Iodide.Experimental, Vet Approved
ArbekacinArbekacin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational
BekanamycinBekanamycin may increase the respiratory depressant activities of Metocurine Iodide.Experimental
Botulinum Toxin Type ABotulinum Toxin Type A may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Investigational
Botulinum Toxin Type BMetocurine Iodide may increase the neuromuscular blocking activities of Botulinum Toxin Type B.Approved
BumetanideBumetanide may decrease the neuromuscular blocking activities of Metocurine Iodide.Approved
CapreomycinCapreomycin may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
ChlortetracyclineChlortetracycline may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Investigational, Vet Approved
ClindamycinClindamycin may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Vet Approved
ColistimethateColistimethate may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Vet Approved
CyclosporineCyclosporine may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Investigational, Vet Approved
CymarinMetocurine Iodide may increase the arrhythmogenic activities of Cymarin.Experimental
DaunorubicinDaunorubicin may increase the respiratory depressant activities of Metocurine Iodide.Approved
DemeclocyclineDemeclocycline may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
DeslanosideMetocurine Iodide may increase the arrhythmogenic activities of Deslanoside.Approved
DibekacinDibekacin may increase the respiratory depressant activities of Metocurine Iodide.Experimental
DigitoxinMetocurine Iodide may increase the arrhythmogenic activities of Digitoxin.Approved, Investigational
DigoxinMetocurine Iodide may increase the arrhythmogenic activities of Digoxin.Approved
Digoxin Immune Fab (Ovine)Metocurine Iodide may increase the arrhythmogenic activities of Digoxin Immune Fab (Ovine).Approved
DihydrostreptomycinDihydrostreptomycin may increase the respiratory depressant activities of Metocurine Iodide.Investigational, Vet Approved
DoxorubicinDoxorubicin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational
DoxycyclineDoxycycline may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Investigational, Vet Approved
EpirubicinEpirubicin may increase the respiratory depressant activities of Metocurine Iodide.Approved
Etacrynic acidEtacrynic acid may decrease the neuromuscular blocking activities of Metocurine Iodide.Approved
FramycetinFramycetin may increase the respiratory depressant activities of Metocurine Iodide.Approved
FurosemideFurosemide may decrease the neuromuscular blocking activities of Metocurine Iodide.Approved, Vet Approved
GeneticinGeneticin may increase the respiratory depressant activities of Metocurine Iodide.Experimental
GentamicinGentamicin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Vet Approved
GENTAMICIN C1AGENTAMICIN C1A may increase the respiratory depressant activities of Metocurine Iodide.Experimental
GitoformateMetocurine Iodide may increase the arrhythmogenic activities of Gitoformate.Experimental
GPX-150GPX-150 may increase the respiratory depressant activities of Metocurine Iodide.Investigational
Hygromycin BHygromycin B may increase the respiratory depressant activities of Metocurine Iodide.Vet Approved
IdarubicinIdarubicin may increase the respiratory depressant activities of Metocurine Iodide.Approved
INNO-206INNO-206 may increase the respiratory depressant activities of Metocurine Iodide.Investigational
IsepamicinIsepamicin may increase the respiratory depressant activities of Metocurine Iodide.Experimental
KanamycinKanamycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational, Vet Approved
Lanatoside CMetocurine Iodide may increase the arrhythmogenic activities of Lanatoside C.Experimental
LincomycinLincomycin may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Vet Approved
LithiumLithium may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
Magnesium HydroxideMagnesium Hydroxide may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
Magnesium oxideMagnesium oxide may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
Magnesium salicylateMagnesium salicylate may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
Magnesium SulfateMagnesium Sulfate may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Vet Approved
MetildigoxinMetocurine Iodide may increase the arrhythmogenic activities of Metildigoxin.Experimental
MetrizamideMetrizamide may increase the respiratory depressant activities of Metocurine Iodide.Approved
MicronomicinMicronomicin may increase the respiratory depressant activities of Metocurine Iodide.Experimental
MinocyclineMinocycline may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Investigational
NeamineNeamine may increase the respiratory depressant activities of Metocurine Iodide.Experimental
NeomycinNeomycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Vet Approved
NetilmicinNetilmicin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational
OleandrinMetocurine Iodide may increase the arrhythmogenic activities of Oleandrin.Experimental, Investigational
OuabainMetocurine Iodide may increase the arrhythmogenic activities of Ouabain.Approved
ParomomycinParomomycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational
PeruvosideMetocurine Iodide may increase the arrhythmogenic activities of Peruvoside.Experimental
PirarubicinPirarubicin may increase the respiratory depressant activities of Metocurine Iodide.Investigational
PiretanidePiretanide may decrease the neuromuscular blocking activities of Metocurine Iodide.Experimental
PirlimycinPirlimycin may increase the neuromuscular blocking activities of Metocurine Iodide.Vet Approved
PlazomicinPlazomicin may increase the respiratory depressant activities of Metocurine Iodide.Investigational
PlicamycinPlicamycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational, Withdrawn
Polymyxin B SulfatePolymyxin B Sulfate may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Vet Approved
ProcainamideProcainamide may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
ProscillaridinMetocurine Iodide may increase the arrhythmogenic activities of Proscillaridin.Experimental
PuromycinPuromycin may increase the respiratory depressant activities of Metocurine Iodide.Experimental
QuinidineQuinidine may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
QuinineQuinine may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
RibostamycinRibostamycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational
SabarubicinSabarubicin may increase the respiratory depressant activities of Metocurine Iodide.Investigational
SisomicinSisomicin may increase the respiratory depressant activities of Metocurine Iodide.Investigational
SP1049CSP1049C may increase the respiratory depressant activities of Metocurine Iodide.Investigational
SpectinomycinSpectinomycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational, Vet Approved
StreptomycinStreptomycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Vet Approved
StreptozocinStreptozocin may increase the respiratory depressant activities of Metocurine Iodide.Approved
TobramycinTobramycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational
TorasemideTorasemide may decrease the neuromuscular blocking activities of Metocurine Iodide.Approved
ValrubicinValrubicin may increase the respiratory depressant activities of Metocurine Iodide.Approved
VancomycinVancomycin may increase the neuromuscular blocking activities of Metocurine Iodide.Approved
Zoptarelin doxorubicinZoptarelin doxorubicin may increase the respiratory depressant activities of Metocurine Iodide.Investigational
ZorubicinZorubicin may increase the respiratory depressant activities of Metocurine Iodide.Experimental
Food Interactions
Not Available

References

Synthesis Reference

Bray, M.D.; U.S. Patent 2,581,903; January 8, 1952; assigned to Eli Lilly and Company.

General References
Not Available
External Links
Human Metabolome Database
HMDB14560
KEGG Drug
D00761
PubChem Compound
24244
PubChem Substance
46507773
ChemSpider
22666
ChEBI
6901
ChEMBL
CHEMBL1739
Therapeutic Targets Database
DAP000824
PharmGKB
PA164749507

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntravenous2 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)267-270Bray, M.D.; U.S. Patent 2,581,903; January 8, 1952; assigned to Eli Lilly and Company.
Predicted Properties
PropertyValueSource
Water Solubility0.000123 mg/mLALOGPS
logP0.81ALOGPS
logP-1.8ChemAxon
logS-6.9ALOGPS
pKa (Strongest Acidic)12.99ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area55.38 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity211.94 m3·mol-1ChemAxon
Polarizability73.46 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9112
Blood Brain Barrier+0.9374
Caco-2 permeable+0.6898
P-glycoprotein substrateSubstrate0.8261
P-glycoprotein inhibitor INon-inhibitor0.6293
P-glycoprotein inhibitor IINon-inhibitor0.7474
Renal organic cation transporterNon-inhibitor0.5766
CYP450 2C9 substrateNon-substrate0.826
CYP450 2D6 substrateNon-substrate0.6251
CYP450 3A4 substrateSubstrate0.6945
CYP450 1A2 substrateNon-inhibitor0.8688
CYP450 2C9 inhibitorNon-inhibitor0.9391
CYP450 2D6 inhibitorNon-inhibitor0.8916
CYP450 2C19 inhibitorNon-inhibitor0.8992
CYP450 3A4 inhibitorNon-inhibitor0.8879
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9634
Ames testAMES toxic0.5764
CarcinogenicityNon-carcinogens0.8865
BiodegradationNot ready biodegradable0.9867
Rat acute toxicity2.7013 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8502
hERG inhibition (predictor II)Non-inhibitor0.6006
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 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

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 zwitterions / Organic iodide salts
show 1 more
Substituents
Diaryl ether / Tetrahydroisoquinoline / Anisole / Alkyl aryl ether / Aralkylamine / Benzenoid / Tetraalkylammonium salt / Quaternary ammonium salt / Oxacycle / Azacycle
show 10 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

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. 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. 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]
  4. Iwatsuki N, Hashimoto Y, Amaha K, Obara S, Iwatsuki K: Inotropic effects of non-depolarizing muscle relaxants in isolated canine heart muscle. Anesth Analg. 1980 Oct;59(10):717-21. [PubMed:6107062]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:37