Identification

Name
Tubocurarine
Accession Number
DB01199
Description

Tubocurarine is a non-depolarizing neuromuscular blocking agent and the first identified curare alkaloid.1 Curare is one of the names used to describe plant-derived poisons used by indigenous South Americans to coat the tips of hunting arrows and darts, which were typically derived from plants of the genera Chondrodendron and Strychnos.1 Tubocurarine is a benzylisoquinoline derivative and shares this structural backbone with a number of plant-derived alkaloids, including morphine and papaverine.2 It was first isolated by Harold King in 1935 and was used clinically to induce neuromuscular blockade during surgeries, particularly those involving the abdomen.4 Tubocurarine's clinical use was limited by its relatively long duration of action (30-60 minutes)4 and a number of significant side effects.6 Safer and more pharmacokinetically favorable non-depolarizing neuromuscular blockers, such as rocuronium, have largely replaced the use of tubocurarine in the clinical setting.6

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 609.7312
Monoisotopic: 609.296462054
Chemical Formula
C37H41N2O6
Synonyms
  • (+)-tubocurarine
  • 7',12'-dihydroxy-6,6'-dimethoxy-2,2',2'-trimethyltubocuraranium
  • d-tubocurarine
  • Tubocurarin
  • Tubocurarine
  • Tubocurarinum

Pharmacology

Indication
Not Available
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics
Not Available
Mechanism of action

Tubocurarine exerts its neuromuscular blocking effects via inhibition of acetylcholine (ACh) activity.1 It exerts a sort of reversible competitive antagonistic effect at post-synaptic nicotinic receptors, reducing the probability of activation via ACh by repeatedly associating and dissociating from these receptors - in doing so, tubocurarine prevents depolarization of the affected nerves. This mechanism distinguishes tubocurarine and similars from other neuromuscular blocking agents and is the reason they are referred to as "non-depolarizing neuromuscular blockers".1

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
antagonist
Humans
A5-hydroxytryptamine receptor 3A
antagonist
Humans
UAcetylcholinesterase
inhibitor
Humans
UNeuronal acetylcholine receptor subunit alpha-7Not AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life

1-2 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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
AcebutololTubocurarine may increase the bradycardic activities of Acebutolol.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Tubocurarine.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Tubocurarine.
AcetylcholineThe risk or severity of adverse effects can be increased when Tubocurarine is combined with Acetylcholine.
AcetyldigitoxinThe risk or severity of Cardiac Arrhythmia can be increased when Tubocurarine is combined with Acetyldigitoxin.
AclidiniumTubocurarine may increase the neuromuscular blocking activities of Aclidinium.
AcyclovirThe risk or severity of adverse effects can be increased when Acyclovir is combined with Tubocurarine.
AgomelatineThe risk or severity of adverse effects can be increased when Tubocurarine is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Tubocurarine.
AlimemazineThe risk or severity of adverse effects can be increased when Tubocurarine is combined with Alimemazine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Product Ingredients
IngredientUNIICASInChI Key
Tubocurarine chloride pentahydrate900961Z8VR6989-98-6WMIZITXEJNQAQK-GGDSLZADSA-N
International/Other Brands
Tubarine
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Tubocurarine Chloride Inj 3mg/mlSolutionIntravenousAbbott1951-12-312008-06-06Canada flag
Tubocurarine Chloride Inj 3mg/ml USPSolutionIntramuscular; IntravenousAbbott1985-12-312008-06-06Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
M03AA02 — Tubocurarine
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 / 1-hydroxy-2-unsubstituted benzenoids / Tetraalkylammonium salts / Trialkylamines / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Diaryl ether / Hydrocarbon derivative
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzylisoquinoline alkaloid (CHEBI:9774) / Isoquinoline alkaloids (C07547)

Chemical Identifiers

UNII
W9YXS298BM
CAS number
57-95-4
InChI Key
JFJZZMVDLULRGK-URLMMPGGSA-O
InChI
InChI=1S/C37H40N2O6/c1-38-14-12-24-19-32(42-4)33-21-27(24)28(38)16-22-6-9-26(10-7-22)44-37-35-25(20-34(43-5)36(37)41)13-15-39(2,3)29(35)17-23-8-11-30(40)31(18-23)45-33/h6-11,18-21,28-29H,12-17H2,1-5H3,(H-,40,41)/p+1/t28-,29+/m0/s1
IUPAC Name
(1S,16R)-9,21-dihydroxy-10,25-dimethoxy-15,15,30-trimethyl-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-dodecaen-15-ium
SMILES
[H][[email protected]@]12CC3=CC=C(OC4=C5C(CC[N+](C)(C)[[email protected]]5([H])CC5=CC(OC6=C(OC)C=C(CCN1C)C2=C6)=C(O)C=C5)=CC(OC)=C4O)C=C3

References

General References
  1. Bowman WC: Neuromuscular block. Br J Pharmacol. 2006 Jan;147 Suppl 1:S277-86. doi: 10.1038/sj.bjp.0706404. [PubMed:16402115]
  2. Singla D, Sharma A, Kaur J, Panwar B, Raghava GP: BIAdb: a curated database of benzylisoquinoline alkaloids. BMC Pharmacol. 2010 Mar 5;10:4. doi: 10.1186/1471-2210-10-4. [PubMed:20205728]
  3. Matteo RS, Lieberman IG, Salanitre E, McDaniel DD, Diaz J: Distribution, elimination, and action of d-tubocurarine in neonates, infants, children, and adults. Anesth Analg. 1984 Sep;63(9):799-804. [PubMed:6465573]
  4. Huang L, Sang CN, Desai MS: A Chronology for the Identification and Disclosure of Adverse Effects of Succinylcholine. J Anesth Hist. 2019 Jul;5(3):65-84. doi: 10.1016/j.janh.2018.07.003. Epub 2018 Jul 29. [PubMed:31570201]
  5. Ball C, Westhorpe R: Muscle relaxants--d-tubocurarine. Anaesth Intensive Care. 2005 Aug;33(4):431. doi: 10.1177/0310057X0503300401. [PubMed:16119481]
  6. Bevan DR: Newer neuromuscular blocking agents. Pharmacol Toxicol. 1994 Jan;74(1):3-9. doi: 10.1111/j.1600-0773.1994.tb01065.x. [PubMed:8159634]
Human Metabolome Database
HMDB0015330
KEGG Compound
C07547
PubChem Compound
6000
PubChem Substance
46505279
ChemSpider
5778
BindingDB
50366799
RxNav
10917
ChEBI
9774
ChEMBL
CHEMBL339427
ZINC
ZINC000003978083
Therapeutic Targets Database
DAP000351
PharmGKB
PA451811
Wikipedia
Tubocurarine_chloride
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Hospira Inc.
Dosage Forms
FormRouteStrength
SolutionIntravenous
SolutionIntramuscular; Intravenous
Prices
Unit descriptionCostUnit
Tubocurarine cl 3 mg/ml vial0.37USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000323 mg/mLALOGPS
logP3.12ALOGPS
logP3.14ChemAxon
logS-6.3ALOGPS
pKa (Strongest Acidic)6.45ChemAxon
pKa (Strongest Basic)8.12ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area80.62 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity187.06 m3·mol-1ChemAxon
Polarizability66.41 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.9757
Blood Brain Barrier+0.7287
Caco-2 permeable+0.6869
P-glycoprotein substrateSubstrate0.8917
P-glycoprotein inhibitor INon-inhibitor0.8855
P-glycoprotein inhibitor IINon-inhibitor0.8385
Renal organic cation transporterNon-inhibitor0.6081
CYP450 2C9 substrateNon-substrate0.8397
CYP450 2D6 substrateNon-substrate0.6012
CYP450 3A4 substrateSubstrate0.6597
CYP450 1A2 substrateNon-inhibitor0.9365
CYP450 2C9 inhibitorNon-inhibitor0.948
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9136
CYP450 3A4 inhibitorNon-inhibitor0.9284
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9794
Ames testNon AMES toxic0.5666
CarcinogenicityNon-carcinogens0.9195
BiodegradationNot ready biodegradable0.9401
Rat acute toxicity2.6331 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8786
hERG inhibition (predictor II)Non-inhibitor0.5444
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-03di-0000090000-3b12a16109f25ee30930
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-03di-0000090000-7ed720c5e8c5ce8facd3

Targets

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. [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. Wenningmann I, Dilger JP: The kinetics of inhibition of nicotinic acetylcholine receptors by (+)-tubocurarine and pancuronium. Mol Pharmacol. 2001 Oct;60(4):790-6. [PubMed:11562442]
  4. Nishimura K, Kitamura Y, Taniguchi T, Agata K: Analysis of motor function modulated by cholinergic neurons in planarian Dugesia japonica. Neuroscience. 2010 Jun 16;168(1):18-30. doi: 10.1016/j.neuroscience.2010.03.038. Epub 2010 Mar 23. [PubMed:20338223]
  5. Jonsson Fagerlund M, Dabrowski M, Eriksson LI: Pharmacological characteristics of the inhibition of nondepolarizing neuromuscular blocking agents at human adult muscle nicotinic acetylcholine receptor. Anesthesiology. 2009 Jun;110(6):1244-52. doi: 10.1097/ALN.0b013e31819fade3. [PubMed:19417616]
  6. 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]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated potassium channel activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
References
  1. Hefft S, Hulo S, Bertrand D, Muller D: Synaptic transmission at nicotinic acetylcholine receptors in rat hippocampal organotypic cultures and slices. J Physiol. 1999 Mar 15;515 ( Pt 3):769-76. [PubMed:10066903]
  2. Yan D, White MM: Interaction of d-tubocurarine analogs with mutant 5-HT(3) receptors. Neuropharmacology. 2002 Sep;43(3):367-73. [PubMed:12243766]
  3. Yan D, Meyer JK, White MM: Mapping residues in the ligand-binding domain of the 5-HT(3) receptor onto d-tubocurarine structure. Mol Pharmacol. 2006 Aug;70(2):571-8. Epub 2006 May 24. [PubMed:16723497]
  4. Peters JA, Malone HM, Lambert JJ: Antagonism of 5-HT3 receptor mediated currents in murine N1E-115 neuroblastoma cells by (+)-tubocurarine. Neurosci Lett. 1990 Mar 2;110(1-2):107-12. [PubMed:1691468]
  5. Emerit MB, Riad M, Fattaccini CM, Hamon M: Characteristics of [14C]guanidinium accumulation in NG 108-15 cells exposed to serotonin 5-HT3 receptor ligands and substance P. J Neurochem. 1993 Jun;60(6):2059-67. [PubMed:7684066]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Radic Z, Taylor P: The influence of peripheral site ligands on the reaction of symmetric and chiral organophosphates with wildtype and mutant acetylcholinesterases. Chem Biol Interact. 1999 May 14;119-120:111-7. [PubMed:10421444]
  2. Golicnik M, Fournier D, Stojan J: Acceleration of Drosophila melanogaster acetylcholinesterase methanesulfonylation: peripheral ligand D-tubocurarine enhances the affinity for small methanesulfonylfluoride. Chem Biol Interact. 2002 Feb 20;139(2):145-57. [PubMed:11823003]
  3. Radic Z, Taylor P: Peripheral site ligands accelerate inhibition of acetylcholinesterase by neutral organophosphates. J Appl Toxicol. 2001 Dec;21 Suppl 1:S13-4. [PubMed:11920914]
  4. Gupta RC, Dettbarn WD: Potential of memantine, D-tubocurarine, and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents: soman, sarin, tabun and VX. Neurotoxicology. 1992 Fall;13(3):649-61. [PubMed:1475066]
  5. Bianchi DA, Hirschmann GS, Theoduloz C, Bracca AB, Kaufman TS: Synthesis of tricyclic analogs of stephaoxocanidine and their evaluation as acetylcholinesterase inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2711-5. [PubMed:15878275]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance 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. The cha...
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight
56448.925 Da
References
  1. Briggs CA, McKenna DG, Monteggia LM, Touma E, Roch JM, Arneric SP, Gopalakrishnan M, Sullivan JP: Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant. Eur J Pharmacol. 1999 Feb 5;366(2-3):301-8. [PubMed:10082212]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Jeffrey K. Aronson (2015). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions (16th ed.). Elsevier. [ISBN:0444537163]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, Arndt P, Lang F, Koepsell H: Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem. 1996 Dec 20;271(51):32599-604. [PubMed:8955087]
  2. Lozano E, Herraez E, Briz O, Robledo VS, Hernandez-Iglesias J, Gonzalez-Hernandez A, Marin JJ: Role of the plasma membrane transporter of organic cations OCT1 and its genetic variants in modern liver pharmacology. Biomed Res Int. 2013;2013:692071. doi: 10.1155/2013/692071. Epub 2013 Jul 31. [PubMed:23984399]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H: Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81. [PubMed:9260930]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2020 03:11

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