You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameMetocurine Iodide
Accession NumberDB00416  (APRD01318)
TypeSmall Molecule
GroupsWithdrawn
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
SynonymLanguageCode
(+)-O,O'-Dimethylchondrocurarine Di-iodideNot AvailableNot Available
Dimethyl Tubocurarine IodideNot AvailableNot Available
Dimethyltubocurarine IodideNot AvailableNot Available
Dimetiltubocurarinio, ioduro deNot AvailableNot Available
Metocurine iodideNot AvailableUSAN
Metocurini IodidumNot AvailableNot Available
MetokuriinijodidiNot AvailableNot Available
MetokurinjodidNot AvailableNot Available
Metubine iodideNot AvailableTN
Trimethyltubocurarine IodideNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
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
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
Pharmacology
IndicationFor use as an anesthesia adjunct to induce skeletal muscle relaxation and to reduce the intensity of muscle contractions in convulsive therapy.
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.
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
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 substrateNon-inhibitor0.9391
CYP450 2D6 substrateNon-inhibitor0.8916
CYP450 2C19 substrateNon-inhibitor0.8992
CYP450 3A4 substrateNon-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
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
PackagersNot Available
Dosage formsNot Available
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
References
Synthesis Reference

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

General ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Neuronal acetylcholine receptor subunit alpha-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Neuronal acetylcholine receptor subunit alpha-2 Q15822 Details

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
  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
  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. Pubmed
  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
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on April 14, 2014 15:35