Identification

Generic Name
Metocurine iodide
DrugBank Accession Number
DB00416
Background

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.

Type
Small Molecule
Groups
Approved, Withdrawn
Structure
Thumb
Weight
Average: 906.6279
Monoisotopic: 906.160174118
Chemical Formula
C40H48I2N2O6
Synonyms
  • Dimethyl tubocurarine iodide
  • Dimethylchondrocurarine iodide
  • Dimethyltubocurarinium iodide
  • Metocurine iodide
  • Metocurini iodidum
  • Metubine iodide
External IDs
  • NSC-36388

Pharmacology

Indication

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

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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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
Humans
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

Adverse Effects
Adverseeffects
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Toxicity

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

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Metocurine iodide is combined with 1,2-Benzodiazepine.
AcetazolamideThe risk or severity of adverse effects can be increased when Metocurine iodide is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Metocurine iodide is combined with Acetophenazine.
AcetyldigitoxinThe risk or severity of Cardiac Arrhythmia can be increased when Metocurine iodide is combined with Acetyldigitoxin.
AclidiniumMetocurine iodide may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Metocurine iodide is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Metocurine iodide is combined with Alfentanil.
AlimemazineThe risk or severity of adverse effects can be increased when Metocurine iodide is combined with Alimemazine.
AlloinThe therapeutic efficacy of Alloin can be decreased when used in combination with Metocurine iodide.
AlmotriptanThe risk or severity of adverse effects can be increased when Metocurine iodide is combined with Almotriptan.
Interactions
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Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Metubine Iodide Inj 2mg/mlLiquid2 mg / mLIntravenousEli Lilly & Co. Ltd.1948-12-311998-08-04Canada flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Diaryl ether / Hydrocarbon derivative / Organic iodide salt
show 10 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
O0U0E87X7F
CAS number
7601-55-0
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

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
Human Metabolome Database
HMDB0014560
KEGG Drug
D00761
PubChem Compound
24244
PubChem Substance
46507773
ChemSpider
22666
RxNav
203206
ChEBI
6901
ChEMBL
CHEMBL1739
Therapeutic Targets Database
DAP000824
PharmGKB
PA164749507
Wikipedia
Metocurine_Iodide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
Not Available
Dosage Forms
FormRouteStrength
LiquidIntravenous2 mg / mL
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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 03, 2021 00:39