Details of the Drug

General Information of Drug (ID: DMBZIVP)

• Drug Name: Tubocurarine
• Synonyms: Amelizol; Delacurarine; Jexin; Tubadil; Tubaine; Tubarine; Tubocurarin; Tubocurarinum; Chlorure de tubocurarine; Cloruro de tubocurarina; Dextrotubocurarine chloride; Intocostrine T; Isoquinoline alkaloid; Tubocurarina cloruro; Tubocurarina cloruro [DCIT]; Tubocurarine chloride; Tubocurarine hydrochloride; Tubocurarini chloridum; Chlorure de tubocurarine [INN-French]; Cloruro de tubocurarina [INN-Spanish]; Curarin-haf; D-Paracurarine chloride; D-Tubocurarine; D-Tubocurarine chloride; D-Tubocurarine dichloride; D-Tubocurarine hydrochloride; Delacurarine (TN); Jex (TN); Metubine (TN); Tubaine (TN); Tubarine (TN); Tubocurarine chloride (INN); Tubocurarine chloride (TN); Tubocurarine chloride (anhydrous); Tubocurarini chloridum [INN-Latin]; Tubocurarinum (TN); D-(+)-Tubocurarine chloride; Tubocurarine, chloride, hydrochloride, (+)-(8CI); D-7',12'-Dihydroxy-6,6'-dimethoxy-2,2',2'-trimethyltubocuraranium chloride; Tubocuraranium, 7',12'-dihydroxy-6,6'-dimethoxy-2,2',2'-trimethyl-, chloride, hydrochloride; (+)-Tubocurarine; (+)-Tubocurarine chloride; (+)-Tubocurarine chloride hydrochloride; 2,2',2'-trimethyl-6,6'-bis(methyloxy)tubocuraran-2,2'-diium-7',12'-diol dichloride; 7',12'-Dihydroxy-6,6'-dimethoxy-2,2',2'-trimethyltubocuraranium; 7',12'-dihydroxy-6,6'-dimethoxy-2,2',2'-trimethyltubocuraran-2'-ium

Indication

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[1]
Smoking dependence	6C4A.2	Approved	[1]

• Therapeutic Class: Neuromuscular Nondepolarizing Agents
• Affected Organisms: Humans and other mammals
• ATC Code:
  M03AA02: Tubocurarine
  M03AA: Curare alkaloids
  M03A: MUSCLE RELAXANTS, PERIPHERALLY ACTING AGENTS
  M03: MUSCLE RELAXANTS
  M: MUSCULO-SKELETAL SYSTEM
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 609.7
  Logarithm of the Partition Coefficient (xlogp); 6
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 3.4 mL/min/kg [3]
  Elimination: 63% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1 - 2 hours [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.09389 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.58% [3]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.45 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 50 mg/mL [2]
• Chemical Identifiers:
  Formula: C37H41N2O6+
  IUPAC Name: (1S,16R)-10,25-dimethoxy-15,15,30-trimethyl-7,23-dioxa-30-aza-15-azoniaheptacyclo[22.6.2.23,6.18,12.118,22.027,31.016,34]hexatriaconta-3(36),4,6(35),8(34),9,11,18(33),19,21,24,26,31-dodecaene-9,21-diol
  Canonical SMILES: CN1CCC2=CC(=C3C=C2[C@@H]1CC4=CC=C(C=C4)OC5=C6[C@@H](CC7=CC(=C(C=C7)O)O3)[N+](CCC6=CC(=C5O)OC)(C)C)OC
  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
  InChIKey: JFJZZMVDLULRGK-URLMMPGGSA-O
• Cross-matching ID:
  PubChem CID: 6000
  ChEBI ID: CHEMBL339427
  CAS Number: 57-95-4
  UNII: W9YXS298BM
  DrugBank ID: DB01199
  TTD ID: D05HSC
  VARIDT ID: DR00536
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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Neuronal acetylcholine receptor alpha-2 (CHRNA2)	TTF4E0J	ACHA2_HUMAN	Antagonist	[5]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Complement component C7 (C7)	OTZ27VJN	CO7_HUMAN	Gene/Protein Processing	[7]
E3 ubiquitin-protein ligase parkin (PRKN)	OTJBN41W	PRKN_HUMAN	Gene/Protein Processing	[7]
Fasciculation and elongation protein zeta-1 (FEZ1)	OTWCXPRE	FEZ1_HUMAN	Gene/Protein Processing	[8]
Golgin subfamily A member 4 (GOLGA4)	OTCMEHNJ	GOGA4_HUMAN	Gene/Protein Processing	[7]
Histone-lysine N-methyltransferase 2C (KMT2C)	OTC59BCO	KMT2C_HUMAN	Gene/Protein Processing	[8]
Ligand-gated cation channel ZACN	OTI241FS	ZACN_HUMAN	Gene/Protein Processing	[9]
Ninein (NIN)	OTVH3M4Z	NIN_HUMAN	Gene/Protein Processing	[7]
Small conductance calcium-activated potassium channel protein 2 (KCNN2)	OTQVTMK5	KCNN2_HUMAN	Gene/Protein Processing	[10]
Son of sevenless homolog 1 (SOS1)	OTTCWXC3	SOS1_HUMAN	Gene/Protein Processing	[7]
Stress-induced-phosphoprotein 1 (STIP1)	OT7TXLOX	STIP1_HUMAN	Gene/Protein Processing	[7]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Tubocurarine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Paromomycin	DM1AGXN	Major	Additive neuromuscular blocking effects by the combination of Tubocurarine and Paromomycin.	Amoebiasis [1A36]	[11]
Fosphenytoin	DMOX3LB	Moderate	Increased metabolism of Tubocurarine caused by Fosphenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Metipranolol	DMJMVKI	Moderate	Additive neuromuscular blocking effects by the combination of Tubocurarine and Metipranolol.	Glaucoma [9C61]	[13]
Levobunolol	DMTNFCQ	Moderate	Additive cardiorespiratory depression effects by the combination of Tubocurarine and Levobunolol.	Glaucoma [9C61]	[13]
Lincomycin	DMVTHER	Moderate	Additive neuromuscular blocking effects by the combination of Tubocurarine and Lincomycin.	Gram-positive bacterial infection [1B74-1F40]	[14]
Nebivolol	DM7F1PA	Moderate	Additive neuromuscular blocking effects by the combination of Tubocurarine and Nebivolol.	Hypertension [BA00-BA04]	[15]
Dexamethasone	DMMWZET	Moderate	Additive neuromuscular blocking effects by the combination of Tubocurarine and Dexamethasone.	Rheumatoid arthritis [FA20]	[16]
Plazomicin	DMKMBES	Major	Additive neuromuscular blocking effects by the combination of Tubocurarine and Plazomicin.	Urinary tract infection [GC08]	[17]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2294).
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [5] Pharmacological characteristics of the inhibition of nondepolarizing neuromuscular blocking agents at human adult muscle nicotinic acetylcholine receptor. Anesthesiology. 2009 Jun;110(6):1244-52.
• [6] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [7] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [8] Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. J Biol Chem. 2003 May 2;278(18):15633-40.
• [9] A novel class of ligand-gated ion channel is activated by Zn2+. J Biol Chem. 2003 Jan 10;278(2):712-7. doi: 10.1074/jbc.M208814200. Epub 2002 Oct 14.
• [10] Ca2+-activated K+ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization. J Biol Chem. 2000 Dec 22;275(51):39954-63. doi: 10.1074/jbc.M001562200.
• [11] Burkett L, Bikhazi GB, Thomas KC Jr, Rosenthal DA, Wirta MG, Foldes FF "Mutual potentiation of the neuromuscular effects of antibiotics and relaxants." Anesth Analg 58 (1979): 107-15. [PMID: 571233]
• [12] Liberman BA, Norman P, Hardy BG "Pancuronium-phenytoin interaction: a case of decreased duration of neuromuscular blockade." Int J Clin Pharmacol Ther Toxicol 26 (1988): 371-4. [PMID: 3220609]
• [13] Harrah MD, Way WL, Katzung BG "The interaction of d-tubocurarine with antiarrhythmic drugs." Anesthesiology 33 (1970): 406-10. [PMID: 5512329]
• [14] Alahdal O, Bevan DR "Clindamycin-induced neuromuscular blockade." Can J Anaesth 42 (1995): 614-7. [PMID: 7553999]
• [15] Chapple DJ, Clark JS, Hughes R "Interaction between atracurium and drugs used in anaesthesia." Br J Anaesth 55 Suppl 1 (1983): s17-22. [PMID: 6688011]
• [16] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [17] Geha DG, Blitt CD, Moon BJ "Prolonged neuromuscular blockade with pancuronium in the presence of acute renal failure: a case report." Anesth Analg 55 (1976): 343-5. [PMID: 945014]