Tubocurarine (original) (raw)

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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

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

Indication

Not Available

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Contraindications & Blackbox Warnings

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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

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

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Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Food Interactions

Not Available

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Product Ingredients

International/Other Brands

Tubarine

Brand Name Prescription Products

ATC Codes

M03AA02 — Tubocurarine

• M03AA — Curare alkaloids
• M03A — MUSCLE RELAXANTS, PERIPHERALLY ACTING AGENTS
• M03 — MUSCLE RELAXANTS
• M — MUSCULO-SKELETAL SYSTEM

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 / Organic salts / Hydrocarbon derivatives / Organic cations show 3 more

Substituents

1-hydroxy-2-unsubstituted benzenoid / Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Diaryl ether / Hydrocarbon derivative / Organic cation / Organic nitrogen compound / Organic salt / Organoheterocyclic compound / Organonitrogen compound / Organopnictogen compound / Oxacycle / Quaternary ammonium salt / Tertiary aliphatic amine / Tertiary amine / Tetraalkylammonium salt / Tetrahydroisoquinoline show 12 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

benzylisoquinoline alkaloid (CHEBI:9774) / Isoquinoline alkaloids (C07547)

Affected organisms

• Humans and other mammals

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

General References

1. Bowman WC: Neuromuscular block. Br J Pharmacol. 2006 Jan;147 Suppl 1:S277-86. doi: 10.1038/sj.bjp.0706404. [Article]
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. [Article]
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. [Article]
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. [Article]
5. Ball C, Westhorpe R: Muscle relaxants--d-tubocurarine. Anaesth Intensive Care. 2005 Aug;33(4):431. doi: 10.1177/0310057X0503300401. [Article]
6. 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

RxNav

10917

ChEBI

9774

ChEMBL

CHEMBL339427

ZINC

ZINC000003978083

Therapeutic Targets Database

DAP000351

PharmGKB

PA451811

Wikipedia

Tubocurarine_chloride

MSDS

Clinical Trials

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View Sample Data

Manufacturers

Not Available

Packagers

• Hospira Inc.

Dosage Forms

Prices

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

State

Solid

Experimental Properties

Not Available

Predicted Properties

Predicted ADMET Features

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Mass Spec (NIST)

Not Available

Spectra

Chromatographic Properties

Collision Cross Sections (CCS)

Targets

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Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General 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

Specific Function

Acetylcholine receptor activity

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. 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]
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. [Article]
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. [Article]
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. [Article]
7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
8. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons

Specific Function

Excitatory extracellular ligand-gated monoatomic ion channel activity

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. [Article]
2. Yan D, White MM: Interaction of d-tubocurarine analogs with mutant 5-HT(3) receptors. Neuropharmacology. 2002 Sep;43(3):367-73. [Article]
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. [Article]
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. [Article]
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. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

General Function

Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis

Specific Function

Acetylcholine binding

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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

General 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 channel is blocked by alpha-bungarotoxin

Specific Function

Acetylcholine binding

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. [Article]

Enzymes

Kind

Protein

Organism

Humans

Pharmacological action

No

Actions

Substrate

General Function

Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters

Specific Function

Acetylcholinesterase activity

Gene Name

BCHE

Uniprot ID

P06276

Uniprot Name

Cholinesterase

Molecular Weight

68417.575 Da

References

1. 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

Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)

Specific Function

(r)-carnitine transmembrane transporter activity

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. [Article]
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. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

General Function

Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)

Specific Function

Acetylcholine transmembrane transporter activity

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. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 02, 2024 07:33