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Identification
NameMetocurine Iodide
Accession NumberDB00416  (APRD01318)
TypeSmall Molecule
GroupsWithdrawn
DescriptionMetocurine 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
Dimetiltubocurarinio, ioduro de
Metocurine iodide
Metocurini Iodidum
Metokuriinijodidi
Metokurinjodid
Metubine iodide
Trimethyltubocurarine Iodide
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Metubine Iodide Inj 2mg/mlLiquid2 mgIntravenousEli Lilly Canada Inc1948-12-311998-08-04Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIO0U0E87X7F
CAS number7601-55-0
WeightAverage: 906.6279
Monoisotopic: 906.160174118
Chemical FormulaC40H48I2N2O6
InChI KeyDIGFQJFCDPKEPF-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][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
IndicationFor 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
PharmacodynamicsMetocurine 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 actionMetocurine 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Neuronal acetylcholine receptor subunit alpha-2Proteinyes
antagonist
HumanQ15822 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding35% in plasma
MetabolismNot Available
Route of eliminationNot Available
Half life3 to 4 hours
ClearanceNot Available
ToxicityExcessive 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinMetocurine Iodide may increase the arrhythmogenic activities of Acetyldigitoxin.Approved
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
AnvirzelMetocurine Iodide may increase the arrhythmogenic activities of Anvirzel.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
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, 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
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
DigitoxinMetocurine Iodide may increase the arrhythmogenic activities of Digitoxin.Approved
DigoxinMetocurine Iodide may increase the arrhythmogenic activities of Digoxin.Approved
DihydrostreptomycinDihydrostreptomycin may increase the respiratory depressant activities of Metocurine Iodide.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
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
KanamycinKanamycin may increase the respiratory depressant 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
MetrizamideMetrizamide may increase the respiratory depressant activities of Metocurine Iodide.Approved
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
OuabainMetocurine Iodide may increase the arrhythmogenic activities of Ouabain.Approved
OxytetracyclineOxytetracycline may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Vet Approved
ParomomycinParomomycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Investigational
PirarubicinPirarubicin may increase the respiratory depressant activities of Metocurine Iodide.Investigational
PiretanidePiretanide may decrease the neuromuscular blocking activities of Metocurine Iodide.Experimental
PlicamycinPlicamycin may increase the respiratory depressant activities of Metocurine Iodide.Approved, 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
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
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, 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
TetracyclineTetracycline may increase the neuromuscular blocking activities of Metocurine Iodide.Approved, Vet 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
ZorubicinZorubicin may increase the respiratory depressant activities of Metocurine Iodide.Experimental
Food InteractionsNot Available
References
Synthesis Reference

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

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
PackagersNot Available
Dosage forms
FormRouteStrength
LiquidIntravenous2 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point267-270Bray, 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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzylisoquinolines. These are organic compounds containing an isoquinoline to which a benzyl group is attached.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoquinolines and derivatives
Sub ClassBenzylisoquinolines
Direct ParentBenzylisoquinolines
Alternative Parents
Substituents
  • Benzylisoquinoline
  • Diaryl ether
  • Tetrahydroisoquinoline
  • Anisole
  • Aralkylamine
  • Alkyl aryl ether
  • Benzenoid
  • Quaternary ammonium salt
  • Oxacycle
  • Azacycle
  • Ether
  • Hydrocarbon derivative
  • Organic iodide salt
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Organic zwitterion
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23