TUBOCURARINE

US Previously Marketed

First approved in 1945

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C37H41N2O6
Molecular Weight	609.7312
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C3C=C1OC4=CC(C[C@@H]5C6=C(OC7=CC=C(C[C@@H]3N(C)CC2)C=C7)C(O)=C(OC)C=C6CC[N+]5(C)C)=CC=C4O

InChI

InChIKey=JFJZZMVDLULRGK-URLMMPGGSA-O

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

HIDE SMILES / InChI

Molecular Formula	C37H40N2O6
Molecular Weight	608.7233
Charge	0
Count

Stereochemistry	EPIMERIC
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://howmed.net/pharmacology/tubocurarine-non-depolarizing-neuromuscular-blocker/ | https://www.drugbank.ca/drugs/DB01199

Tubocurarine, a naturally occurring alkaloid, is used to treat smoking withdrawl syndrom. Tubocurarine, the chief alkaloid in tobacco products, binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. Two types of central nervous system effects are believed to be the basis of Tubocurarine's positively reinforcing properties. A stimulating effect is exerted mainly in the cortex via the locus ceruleus and a reward effect is exerted in the limbic system. At low doses the stimulant effects predominate while at high doses the reward effects predominate. Intermittent intravenous administration of Tubocurarine activates neurohormonal pathways, releasing acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, and ACTH. Tubocurarine competes with acetylcholine for post-synaptic nicotinic NM receptors and blocks them.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Potency
Neuronal acetylcholine receptor; alpha3/beta4 40 Target ID: CHEMBL1907594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15203153	Antagonist 2778	2.0 µM [IC50]
Neuronal acetylcholine receptor; alpha4/beta2 76 Target ID: CHEMBL1907589 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23757208	Antagonist 2778	9.2 µM [IC50]
Neuronal acetylcholine receptor subunit alpha-2 3 Target ID: Q15822 Gene ID: 1135.0 Gene Symbol: CHRNA2 Target Organism: Homo sapiens (Human) Sources: https://www.drugbank.ca/drugs/DB01199 \| https://www.ncbi.nlm.nih.gov/pubmed/11562442	Antagonist 2778
Muscle-type nicotinic acetylcholine receptor 65 Target ID: CHEMBL2362997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18633030	Antagonist 2778	24.0 nM [IC50]
Serotonin 3a (5-HT3a) receptor 46 Target ID: CHEMBL1899 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7790853 \| https://www.ncbi.nlm.nih.gov/pubmed/9680250	Antagonist 2778	84.1 nM [Ki]
Small conductance calcium-activated potassium channel protein 1 5 Target ID: CHEMBL2369 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9287325 \| https://www.ncbi.nlm.nih.gov/pubmed/8781233	Blocker 537	27.0 µM [IC50]
Small conductance calcium-activated potassium channel protein 2 4 Target ID: CHEMBL4469 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10696100	Blocker 537	17.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Myasthenia gravis 21 Sources: http://www.druginfosys.com/drug.aspx?drugcode=742&type=1 https://www.drugs.com/mmx/tubocurarine-chloride.html	Diagnostic		Approved 8429	TUBOCURARINE CHLORIDE Approved Use Tubocurarine is indicated as a diagnostic aid for myasthenia gravis when the results of tests with neostigmine or edrophonium are inconclusive Launch Date 1945

C_max

Value	Dose	Co-administered	Analyte	Population
1.173 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7114542/	16 μg/kg/min other, intravenous dose: 16 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:		TUBOCURARINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
117 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7114542/	16 μg/kg/min other, intravenous dose: 16 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:		TUBOCURARINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
89 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7114542/	16 μg/kg/min other, intravenous dose: 16 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:		TUBOCURARINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 512 OCT2 647 MATE1 306 MATE2 263 BSEP 402 MRP2 383 MRP3 157 MRP4 204 CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 OATP1B1 788 OATP1B3 706	OCT1 327 OCT2 355

Drug as perpetrator

Target	Modality	Activity
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/, https://pubmed.ncbi.nlm.nih.gov/23241029/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	likely [IC50 >100 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTY4NyJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTY4NyJ9fQ%3D%3D	no [IC50 >10 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 133 uM]
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 133 uM]
MRP3 207	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 133 uM]
MATE2 263	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23241029/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 55.5 uM]
OCT1 543	inhibitor 3277 Sources: https://transportal.compbio.ucsf.edu/compounds/tubocurarine/, https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 62.4 uM]
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23241029/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 9.4 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 9.6 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	yes [Inhibition 10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OCT1 327	substrate 3367 Sources: https://go.drugbank.com/drugs/DB01199, https://pubmed.ncbi.nlm.nih.gov/23984399/	yes
OCT2 355	substrate 3367 Sources: https://go.drugbank.com/drugs/DB01199, https://pubmed.ncbi.nlm.nih.gov/9260930/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTY4NyJ9fQ%3D%3D

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9774	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9774
ZINC	ZINC000003978083	http://zinc15.docking.org/substances/ZINC000003978083

PubMed

Title	Date	PubMed
Effects of pretreatment with cisatracurium, rocuronium, and d-tubocurarine on succinylcholine-induced fasciculations and myalgia: a comparison with placebo.	1999 Dec	10680105
Structural features of the ligand-binding domain of the serotonin 5HT3 receptor.	1999 Feb 26	10026168
Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant.	1999 Feb 5	10082212
Ca2+-activated K+ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization.	2000 Dec 22	10991935
Increased sensitivity to depolarization and nondepolarizing neuromuscular blocking agents in young rat hemidiaphragms.	2001 Aug	11506123
Modulation by nitric oxide (NO) of the intensity of non-quantum mediator secretion in neuromuscular junctions in rats.	2001 Jul-Aug	11508498
Action mechanism of betahistine in the vestibular end organs.	2001 Jun	11677837
The initial mode of action of copper on the cardiac physiology of the blue mussel, Mytilus edulis.	2001 Mar	11163428
[Extrarenal effects of furosemide on normal and ischemic cerebral tissue in the rat].	2001 Mar 1-15	11346820
Modulation by estrogens and xenoestrogens of recombinant human neuronal nicotinic receptors.	2001 Nov 2	11711029
The kinetics of inhibition of nicotinic acetylcholine receptors by (+)-tubocurarine and pancuronium.	2001 Oct	11562442
Stimulation of non-alpha7 nicotinic receptors partially protects dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture.	2002	11801364
Mapping the agonist binding site of the nicotinic acetylcholine receptor by cysteine scanning mutagenesis: antagonist footprint and secondary structure prediction.	2002 Feb	11809872
Activity- and target-dependent regulation of large-conductance Ca2+-activated K+ channels in developing chick lumbar motoneurons.	2002 Jan 1	11756490
Modulation by nicotine of the ionic currents in guinea pig ventricular cardiomyocytes. Relatively higher sensitivity to IKr and IKl.	2002 Jul	12616991
New evidence for a presynaptic action of prednisolone at neuromuscular junctions.	2002 Jul	12115947
Characterization of [(125) I]epibatidine binding and nicotinic agonist-mediated (86) Rb(+) efflux in interpeduncular nucleus and inferior colliculus of beta2 null mutant mice.	2002 Jun	12065623
Properties of nicotinic receptors underlying Renshaw cell excitation by alpha-motor neurons in neonatal rat spinal cord.	2002 Jun	12037212
Acetylcholine increases intracellular Ca2+ in taste cells via activation of muscarinic receptors.	2002 Jun	12037167
Nicotine increases hepatic oxygen uptake in the isolated perfused rat liver by inhibiting glycolysis.	2002 Jun	12023521
Effect of glycine on synaptic transmission at the third order giant synapse of the squids Alloteuthis subulata and Loligo vulgaris.	2002 May 31	12023063
Interaction of d-tubocurarine analogs with mutant 5-HT(3) receptors.	2002 Sep	12243766
Nicotinic alpha 7 receptor clusters on hippocampal GABAergic neurons: regulation by synaptic activity and neurotrophins.	2002 Sep 15	12223543
Comparative fading responses induced by mivacurium, cisatracurium, and d-tubocurarine in the evoked muscular compound action potentials of the cat.	2003	12903920
Synthesis and biological evaluation of 16 beta-pyrrolidinosteroidal derivatives.	2003	12642961
A novel class of ligand-gated ion channel is activated by Zn2+.	2003 Jan 10	12381728
Curariform antagonists bind in different orientations to acetylcholine-binding protein.	2003 Jun 20	12682067
Task-dependent presynaptic inhibition.	2003 Mar 1	12629193
Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line.	2003 May 2	12588870

Patents

Sample Use Guides

In Vivo Use Guide

Diagnostic aid (myasthenia gravis) Intravenous, 4 to 33 mcg (0.004 to 0.033 mg) per kg of body weight. Note: It is recommended that the test be terminated within two to three minutes by intravenous injection of 1.5 mg of neostigmine, since the marked exaggeration of myasthenia gravis symptoms may result in prolonged respiratory paralysis.

Route of Administration: Intravenous

In Vitro Use Guide

D-tubocurarine (30 uM), but not alpha-bungarotoxin (alpha-BTX, 0.1 uM), attenuated the nicotine (NIC) (100 uM)-evoked release of 3H-NA.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 14:59:55 GMT 2023` Edited by `admin` on `Fri Dec 15 14:59:55 GMT 2023`
Record UNII	W9YXS298BM
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TUBOCURARINE

Common Name

English

13H-4,6:21,24-DIETHENO-8,12-METHENO-1H-PYRIDO(3',2':14,15)(1,11)DIOXACYCLOEICOSINO(2,3,4-IJ)ISOQUINOLINIUM, 2,3,13A,14,15,16,25,25A-OCTAHYDRO-9,19-DIHYDROXY-18,29-DIMETHOXY-1,14,14-TRIMETHYL-, (13AR,25AS)-

Common Name

English

Tubocurarine [WHO-DD]

Common Name

English

TUBOCURARINE [HSDB]

Common Name

English

TUBOCURARINE ION

Common Name

English

D-TUBOCURARINE

Common Name

English

(+)-TUBOCURARINE

Common Name

English

TUBOCURARINE CATION

Common Name

English

TUBOCURARANIUM, 7',12'-DIHYDROXY-6,6'-DIMETHOXY-2,2',2'-TRIMETHYL-

Common Name

English

TUBOCURARINE [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-ATC

M03AA02