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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
SaltsNot Available
Brand namesNot Available
Brand mixturesNot 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[22.6.2.2^{3,6}.1^{8,12}.1^{18,22}.0^{27,31}.0^{16,34}]hexatriaconta-3,5,8,10,12(34),18(33),19,21,24(32),25,27(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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIsoquinolines and Derivatives
SubclassBenzylisoquinolines
Direct parentBenzylisoquinolines
Alternative parentsDiarylethers; Anisoles; Alkyl Aryl Ethers; Polyamines
Substituentsdiaryl ether; phenol ether; anisole; alkyl aryl ether; benzene; polyamine; ether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzylisoquinolines. These are organic compounds containing an isoquinoline to which a benzyl group is attached.
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
Metabolism
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
Property Value Probability
Human Intestinal Absorption - 0.9112
Blood Brain Barrier + 0.9374
Caco-2 permeable + 0.6898
P-glycoprotein substrate Substrate 0.8261
P-glycoprotein inhibitor I Non-inhibitor 0.6293
P-glycoprotein inhibitor II Non-inhibitor 0.7474
Renal organic cation transporter Non-inhibitor 0.5766
CYP450 2C9 substrate Non-substrate 0.826
CYP450 2D6 substrate Non-substrate 0.6251
CYP450 3A4 substrate Substrate 0.6945
CYP450 1A2 substrate Non-inhibitor 0.8688
CYP450 2C9 substrate Non-inhibitor 0.9391
CYP450 2D6 substrate Non-inhibitor 0.8916
CYP450 2C19 substrate Non-inhibitor 0.8992
CYP450 3A4 substrate Non-inhibitor 0.8879
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9634
Ames test AMES toxic 0.5764
Carcinogenicity Non-carcinogens 0.8865
Biodegradation Not ready biodegradable 0.9867
Rat acute toxicity 2.7013 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8502
hERG inhibition (predictor II) Non-inhibitor 0.6006
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 Solubility0.000123ALOGPS
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
Spectra
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
ResourceLink
KEGG DrugD00761
PubChem Compound24244
PubChem Substance46507773
ChemSpider22666
Therapeutic Targets DatabaseDAP000824
PharmGKBPA164749507
Drug Product Database466948
ATC CodesM03AA04
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

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Drug created on June 13, 2005 07:24 / Updated on April 14, 2014 15:35