Identification
- Generic Name
- Tubocurarine
- DrugBank Accession Number
- DB01199
- Background
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
Structure for Tubocurarine (DB01199)
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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
Target Actions Organism ANeuronal acetylcholine receptor subunit alpha-2 antagonistHumans A5-hydroxytryptamine receptor 3A antagonistHumans UAcetylcholinesterase inhibitorHumans UNeuronal acetylcholine receptor subunit alpha-7 Not Available Humans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Tubocurarine is combined with 1,2-Benzodiazepine. Acebutolol Tubocurarine may increase the bradycardic activities of Acebutolol. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Tubocurarine. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Tubocurarine. Acetylcholine The risk or severity of adverse effects can be increased when Tubocurarine is combined with Acetylcholine. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Tubocurarine chloride pentahydrate 900961Z8VR 6989-98-6 WMIZITXEJNQAQK-GGDSLZADSA-N - International/Other Brands
- Tubarine
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Tubocurarine Chloride Inj 3mg/ml Solution 3 mg / mL Intravenous Abbott 1951-12-31 2008-06-06 Canada 
Tubocurarine Chloride Inj 3mg/ml USP Solution 3 mg / mL Intramuscular; Intravenous Abbott 1985-12-31 2008-06-06 Canada
Categories
- ATC Codes
- M03AA02 — Tubocurarine
- Drug Categories
- Alkaloids
- Amines
- Anticholinergic Agents
- Benzylisoquinolines
- Central Nervous System Depressants
- Cholinergic Agents
- Cholinesterase Inhibitors
- Cholinesterase substrates
- Curare Alkaloids
- Ganglion Blockers
- Heterocyclic Compounds, Fused-Ring
- Isoquinolines
- Muscle Relaxants
- Muscle Relaxants, Peripherally Acting Agents
- Musculo-Skeletal System
- Neuromuscular Agents
- Neuromuscular Blocking Agents
- Neuromuscular-Blocking Agents (Nondepolarizing)
- Neurotoxic agents
- Neurotransmitter Agents
- Nicotinic Antagonists
- OCT1 substrates
- Onium Compounds
- Peripheral Nervous System Agents
- Quaternary Ammonium Compounds
- Tetrahydroisoquinolines
- 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)
- Affected organisms
- Humans and other mammals
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[22.6.2.2^{3,6}.1^{8,12}.1^{18,22}.0^{27,31}.0^{16,34}]hexatriaconta-3,5,8(34),9,11,18(33),19,21,24,26,31,35-dodecaen-15-ium
- SMILES
- [H][C@@]12CC3=CC=C(OC4=C5C(CC[N+](C)(C)[C@]5([H])CC5=CC(OC6=C(OC)C=C(CCN1C)C2=C6)=C(O)C=C5)=CC(OC)=C4O)C=C3
References
- General References
- Bowman WC: Neuromuscular block. Br J Pharmacol. 2006 Jan;147 Suppl 1:S277-86. doi: 10.1038/sj.bjp.0706404. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Ball C, Westhorpe R: Muscle relaxants--d-tubocurarine. Anaesth Intensive Care. 2005 Aug;33(4):431. doi: 10.1177/0310057X0503300401. [Article]
- Bevan DR: Newer neuromuscular blocking agents. Pharmacol Toxicol. 1994 Jan;74(1):3-9. doi: 10.1111/j.1600-0773.1994.tb01065.x. [Article]
- External Links
- Human Metabolome Database
- HMDB0015330
- KEGG Compound
- C07547
- PubChem Compound
- 6000
- PubChem Substance
- 46505279
- ChemSpider
- 5778
- BindingDB
- 50366799
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Hospira Inc.
- Dosage Forms
Form Route Strength Solution Intravenous 3 mg / mL Solution Intramuscular; Intravenous 3 mg / mL - Prices
Unit description Cost Unit Tubocurarine cl 3 mg/ml vial 0.37USD 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
Property Value Source Water Solubility 0.000323 mg/mL ALOGPS logP 3.12 ALOGPS logP 3.23 Chemaxon logS -6.3 ALOGPS pKa (Strongest Acidic) 8.54 Chemaxon pKa (Strongest Basic) 7.98 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 80.62 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 187.06 m3·mol-1 Chemaxon Polarizability 67.43 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9757 Blood Brain Barrier + 0.7287 Caco-2 permeable + 0.6869 P-glycoprotein substrate Substrate 0.8917 P-glycoprotein inhibitor I Non-inhibitor 0.8855 P-glycoprotein inhibitor II Non-inhibitor 0.8385 Renal organic cation transporter Non-inhibitor 0.6081 CYP450 2C9 substrate Non-substrate 0.8397 CYP450 2D6 substrate Non-substrate 0.6012 CYP450 3A4 substrate Substrate 0.6597 CYP450 1A2 substrate Non-inhibitor 0.9365 CYP450 2C9 inhibitor Non-inhibitor 0.948 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9136 CYP450 3A4 inhibitor Non-inhibitor 0.9284 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9794 Ames test Non AMES toxic 0.5666 Carcinogenicity Non-carcinogens 0.9195 Biodegradation Not ready biodegradable 0.9401 Rat acute toxicity 2.6331 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8786 hERG inhibition (predictor II) Non-inhibitor 0.5444
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 251.2456291 predictedDarkChem Lite v0.1.0 [M-H]- 250.9698291 predictedDarkChem Lite v0.1.0 [M-H]- 245.9191291 predictedDarkChem Lite v0.1.0 [M-H]- 240.99449 predictedDeepCCS 1.0 (2019) [M+H]+ 246.8450291 predictedDarkChem Lite v0.1.0 [M+H]+ 251.3768291 predictedDarkChem Lite v0.1.0 [M+H]+ 245.8143291 predictedDarkChem Lite v0.1.0 [M+H]+ 242.81938 predictedDeepCCS 1.0 (2019) [M+Na]+ 247.2929291 predictedDarkChem Lite v0.1.0 [M+Na]+ 252.7068291 predictedDarkChem Lite v0.1.0 [M+Na]+ 245.2690291 predictedDarkChem Lite v0.1.0 [M+Na]+ 248.42522 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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]
- Wenningmann I, Dilger JP: The kinetics of inhibition of nicotinic acetylcholine receptors by (+)-tubocurarine and pancuronium. Mol Pharmacol. 2001 Oct;60(4):790-6. [Article]
- 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. [Article]
- 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. [Article]
- 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]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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
- 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. [Article]
- Yan D, White MM: Interaction of d-tubocurarine analogs with mutant 5-HT(3) receptors. Neuropharmacology. 2002 Sep;43(3):367-73. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- Radic Z, Taylor P: Peripheral site ligands accelerate inhibition of acetylcholinesterase by neutral organophosphates. J Appl Toxicol. 2001 Dec;21 Suppl 1:S13-4. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
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
- Aronson JK (2016). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions (16th ed.). Amsterdam : Elsevier Science. [ISBN:9780444537164]
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
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:50