TUBOCURARINE

US Previously Marketed

First approved in 1945

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C37H41N2O6
Molecular Weight	609.7326
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCc2cc(c3cc2[C@]1([H])Cc4ccc(cc4)Oc5c6c(CC[N+](C)(C)[C@]6([H])Cc7ccc(c(c7)O3)O)cc(c5O)OC)OC

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	608.7247
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 38 Target ID: CHEMBL1907594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15203153	Antagonist 2575	2.0 µM [IC50]
Neuronal acetylcholine receptor; alpha4/beta2 62 Target ID: CHEMBL1907589 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23757208	Antagonist 2575	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 2575
Muscle-type nicotinic acetylcholine receptor 64 Target ID: CHEMBL2362997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18633030	Antagonist 2575	24.0 nM [IC50]
Serotonin 3a (5-HT3a) receptor 44 Target ID: CHEMBL1899 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7790853 \| https://www.ncbi.nlm.nih.gov/pubmed/9680250	Antagonist 2575	84.1 nM [Ki]
Small conductance calcium-activated potassium channel protein 1 4 Target ID: CHEMBL2369 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9287325 \| https://www.ncbi.nlm.nih.gov/pubmed/8781233	Blocker 511	27.0 µM [IC50]
Small conductance calcium-activated potassium channel protein 2 3 Target ID: CHEMBL4469 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10696100	Blocker 511	17.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Myasthenia gravis 20 Sources: http://www.druginfosys.com/drug.aspx?drugcode=742&type=1 https://www.drugs.com/mmx/tubocurarine-chloride.html	Diagnostic		Approved 8043	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 -7.8459837E11

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 1467	inhibitor 1604	inhibitor 1702	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 480 OCT2 594 MATE1 290 MATE2 251 BSEP 376 MRP2 346 MRP3 150 MRP4 194 CYP1A2 1383 CYP2A6 627 CYP2C19 1325 CYP2E1 790 OATP1B1 733 OATP1B3 657	OCT1 302 OCT2 316

Drug as perpetrator

Target	Modality	Activity
OCT2 595	inhibitor 3045 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 1532	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP2A6 659	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP2C19 1392	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP2C9 1648	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP2D6 1738	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTY4NyJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2E1 871	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	no [IC50 >10 uM]
CYP3A4 1772	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTY4NyJ9fQ%3D%3D	no [IC50 >10 uM]
BSEP 377	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 133 uM]
MRP2 434	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 133 uM]
MRP3 200	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50424714	yes [IC50 133 uM]
MATE2 251	inhibitor 3045 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 495	inhibitor 3045 Sources: https://transportal.compbio.ucsf.edu/compounds/tubocurarine/, https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 62.4 uM]
MATE1 292	inhibitor 3045 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 226	inhibitor 3045 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 748	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2ODcifX0%3D	yes [Inhibition 10 uM]
OATP1B3 666	inhibitor 3045 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 302	substrate 3113 Sources: https://go.drugbank.com/drugs/DB01199, https://pubmed.ncbi.nlm.nih.gov/23984399/	yes
OCT2 316	substrate 3113 Sources: https://go.drugbank.com/drugs/DB01199, https://pubmed.ncbi.nlm.nih.gov/9260930/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 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
Comparison of gallamine with d-tubocurarine effects on fasciculations after succinylcholine.	1975 Jan-Feb	1167766
Structural features of the ligand-binding domain of the serotonin 5HT3 receptor.	1999 Feb 26	10026168
Chick optic lobe contains a developmentally regulated alpha2alpha5beta2 nicotinic receptor subtype.	2000 Aug	10908297
Cloning, expression, and characterization of ferret 5-HT(3) receptor subunit.	2000 Jul 7	10884508
[Effects of non-depolarizing muscle relaxants on the duration of mivacurium].	2001	11510427
Effect of cholinergic agonists on resting membrane potential of earthworm body wall muscle cells.	2001 Apr	11550037
Giant multimodal heart motoneurons of Achatina fulica: a new cardioregulatory input in pulmonates.	2001 Aug	11672694
Differential effects of chronic drug treatment on alpha3* and alpha7 nicotinic receptor binding sites, in hippocampal neurones and SH-SY5Y cells.	2001 Aug	11498514
Cholinergic transmission via central synapses in the locust nervous system.	2001 Dec	11800039
Modulation by nitric oxide (NO) of the intensity of non-quantum mediator secretion in neuromuscular junctions in rats.	2001 Jul-Aug	11508498
Pharmacological characterisation of the human small conductance calcium-activated potassium channel hSK3 reveals sensitivity to tricyclic antidepressants and antipsychotic phenothiazines.	2001 May	11369031
Ongoing nicotinic and non-nicotinic inputs to inhibitory neurons in the mouse colon.	2001 Oct	11553017
Stimulation of non-alpha7 nicotinic receptors partially protects dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture.	2002	11801364
Evaluation of the cholinomimetic actions of trimethylsulfonium, a compound present in the midgut gland of the sea hare Aplysia brasiliana (Gastropoda, Opisthobranchia).	2002 Apr	11960200
The nature of the acetylcholine and 5-hydroxytryptamine receptors in buccal smooth muscle of the pest slug Deroceras reticulatum.	2002 Apr	11919705
Electrophysiological analysis of synaptic transmission in central neurons of Drosophila larvae.	2002 Aug	12163536
Impairment of synaptic vesicle exocytosis and recycling during neuromuscular weakness produced in mice by 2,4-dithiobiuret.	2002 Dec	12466444
Modulation by nicotine of the ionic currents in guinea pig ventricular cardiomyocytes. Relatively higher sensitivity to IKr and IKl.	2002 Jul	12616991
Acetylcholine increases intracellular Ca2+ in taste cells via activation of muscarinic receptors.	2002 Jun	12037167
Activation of embryonic red and white muscle fibers during fictive swimming in the developing zebrafish.	2002 Mar	11877498
Characterization of an apamin-sensitive small-conductance Ca(2+)-activated K(+) channel in porcine coronary artery endothelium: relevance to EDHF.	2002 Mar	11877319
The potency of new muscle relaxants on recombinant muscle-type acetylcholine receptors.	2002 Mar	11867382
Neuromuscular action of Bothrops lanceolatus (Fer de lance) venom and a caseinolytic fraction.	2002 Sep	12220713
Nicotinic alpha 7 receptor clusters on hippocampal GABAergic neurons: regulation by synaptic activity and neurotrophins.	2002 Sep 15	12223543
Curariform antagonists bind in different orientations to the nicotinic receptor ligand binding domain.	2003 Aug 22	12799358
A novel class of ligand-gated ion channel is activated by Zn2+.	2003 Jan 10	12381728
Neuromuscular transmission of pectoral fin muscles of the goldfish Carassius auratus.	2003 Jul	12829051
Dopaminergic excitation of the goat carotid body is mediated by the serotonin type 3 receptor subtype.	2003 Jun 12	12809794
Pharmacological characterization of recombinant bovine alpha3beta4 neuronal nicotinic receptors stably expressed in HEK 293 cells.	2003 Jun 12	12770692
Curariform antagonists bind in different orientations to acetylcholine-binding protein.	2003 Jun 20	12682067
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 `Sat Jun 26 10:31:41 UTC 2021` Edited by `admin` on `Sat Jun 26 10:31:41 UTC 2021`
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 [HSDB]

Common Name

English

TUBOCURARINE ION

Common Name

English

D-TUBOCURARINE

Common Name

English

(+)-TUBOCURARINE

Common Name

English

TUBOCURARINE [WHO-DD]

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