Identification

Name
Metocurine Iodide
Accession Number
DB00416  (APRD01318)
Type
Small Molecule
Groups
Approved, Withdrawn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][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

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

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
DrugInteraction
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Metocurine Iodide.
AcetyldigitoxinMetocurine Iodide may increase the arrhythmogenic activities of Acetyldigitoxin.
AcetyldigoxinMetocurine Iodide may increase the arrhythmogenic activities of Acetyldigoxin.
AgmatineAgmatine may increase the neuromuscular blocking activities of Metocurine Iodide.
AlclometasoneThe risk or severity of myopathy and weakness can be increased when Metocurine Iodide is combined with Alclometasone.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Metocurine Iodide.
AlimemazineThe risk or severity of adverse effects can be increased when Metocurine Iodide is combined with Alimemazine.
AlmotriptanThe risk or severity of adverse effects can be increased when Metocurine Iodide is combined with Almotriptan.
AlosetronThe risk or severity of adverse effects can be increased when Metocurine Iodide is combined with Alosetron.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Metocurine Iodide.
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
HMDB0014560
KEGG Drug
D00761
PubChem Compound
24244
PubChem Substance
46507773
ChemSpider
22666
ChEBI
6901
ChEMBL
CHEMBL1739
Therapeutic Targets Database
DAP000824
PharmGKB
PA164749507
Wikipedia
Metocurine_Iodide

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 October 01, 2018 12:47