Details of the Drug

General Information of Drug (ID: DMGP8AX)

Drug Name

Thiopental

Synonyms

Intraval; Penthiobarbital; Pentothiobarbital; Thiomebumal; Thionembutal; Thiopentobarbital; Thiopentobarbitone; Thiopentone; Thiothal; Tiopentale; Trapanal; Thiopental [BAN]; Thiopental solution; Thiopentobarbituric acid; Tiopentale [Italian]; Sodium Pentothal (TN); Thiopental (TN); Thiopentone sodium (TN); Trapanal (TN); (+-)-Thiopental; (+/-)-THIOPENTAL; (+/-)-Thiopental solution; 2-Thio-5-ethyl-5-sec-pentylbarbituric acid; 4,6,(1H,5H)-Pyrimidinedione, 5-ethyldihydro-5-(1-methylbutyl)-2-thioxo-(9CI); 5-Ethyl-5-(1-methyl-butyl)-2-thioxo-dihydro-pyrimidine-4,6-dione; 5-Ethyl-5-(1-methylbutyl)-2-thiobarbituric acid; 5-ethyl-2-mercapto-5-(1-methylbutyl)pyrimidine-4,6(1H,5H)-dione; 5-ethyl-5-(1-methylbutyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; 5-ethyl-5-pentan-2-yl-2-sulfanylidene-1,3-diazinane-4,6-dione

Indication

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[1]
Epilepsy	8A60-8A68	Approved	[2]
Pseudotumor cerebri	N.A.	Approved	[2]
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Therapeutic Class

Hypnotics and Sedatives

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

242.34

Logarithm of the Partition Coefficient (xlogp)

2.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is rapidly absorbed []
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Clearance: The drug present in the plasma can be removed from the body at the rate of 8.2 mL/min/kg [4]
Elimination: 0.5% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 3 - 8 hours [4]
Metabolism: The drug is metabolized via the liver [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 20.632 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.14% [4]
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 1.2 L/kg [4]
Water Solubility: The ability of drug to dissolve in water is measured as 50 mg/mL [3]

Chemical Identifiers

Formula: C11H18N2O2S
IUPAC Name: 5-ethyl-5-pentan-2-yl-2-sulfanylidene-1,3-diazinane-4,6-dione
Canonical SMILES: CCCC(C)C1(C(=O)NC(=S)NC1=O)CC
InChI: InChI=1S/C11H18N2O2S/c1-4-6-7(3)11(5-2)8(14)12-10(16)13-9(11)15/h7H,4-6H2,1-3H3,(H2,12,13,14,15,16)
InChIKey: IUJDSEJGGMCXSG-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3000715
ChEBI ID: CHEBI:102166
CAS Number: 76-75-5
DrugBank ID: DB00599
TTD ID: D00MYT
INTEDE ID: DR1580

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fatty acid amide hydrolase (FAAH)	TTDP1UC	NOUNIPROTAC	Inhibitor	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Mephenytoin 4-hydroxylase (CYP2C19)_{Main DME}	DEGTFWK	CP2CJ_HUMAN	Substrate	[8]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Gene/Protein Processing	[9]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[10]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Gene/Protein Processing	[11]
Heat shock protein beta-1 (HSPB1)	OTHFZ8ED	HSPB1_HUMAN	Gene/Protein Processing	[11]
Heat shock protein HSP 90-alpha (HSP90AA1)	OTLG1WPK	HS90A_HUMAN	Gene/Protein Processing	[11]
Interleukin-2 receptor subunit alpha (IL2RA)	OT0MWCHG	IL2RA_HUMAN	Protein Interaction/Cellular Processes	[12]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Protein Interaction/Cellular Processes	[13]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Anaesthesia

ICD Disease Classification

9A78.6

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Fatty acid amide hydrolase (FAAH)	DTT	NO-GeName	2.65E-01	0.02	0.1
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.66E-01	9.19E-03	4.88E-02

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Thiopental

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Propofol	DMB4OLE	Moderate	Additive CNS depression effects by the combination of Thiopental and Propofol.	Corneal disease [9A76-9A78]	[14]
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Coadministration of a Drug Treating the Disease Different from Thiopental (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mitotane	DMU1GX0	Minor	Increased metabolism of Thiopental caused by Mitotane mediated induction of CYP450 enzyme.	Adrenal cancer [2D11]	[15]
Nifedipine	DMSVOZT	Moderate	Increased metabolism of Thiopental caused by Nifedipine mediated induction of CYP450 enzyme.	Angina pectoris [BA40]	[16]
Aminophylline	DML2NIB	Moderate	Increased metabolism of Thiopental caused by Aminophylline mediated induction of CYP450 enzyme.	Asthma [CA23]	[17]
Olopatadine	DMKMWQG	Moderate	Additive CNS depression effects by the combination of Thiopental and Olopatadine.	Conjunctiva disorder [9A60]	[18]
Ethanol	DMDRQZU	Major	Additive CNS depression effects by the combination of Thiopental and Ethanol.	Cystitis [GC00]	[19]
Paroxetine	DM5PVQE	Minor	Increased metabolism of Thiopental caused by Paroxetine mediated induction of CYP450 enzyme.	Depression [6A70-6A7Z]	[20]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Thiopental and Esketamine.	Depression [6A70-6A7Z]	[21]
Nicardipine	DMCDYW7	Moderate	Increased metabolism of Thiopental caused by Nicardipine mediated induction of CYP450 enzyme.	Essential hypertension [BA00]	[16]
Rifampin	DMA8J1G	Minor	Increased metabolism of Thiopental caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[22]
Levamlodipine	DM92S6N	Moderate	Increased metabolism of Thiopental caused by Levamlodipine mediated induction of CYP450 enzyme.	Hypertension [BA00-BA04]	[16]
Verapamil	DMA7PEW	Moderate	Increased metabolism of Thiopental caused by Verapamil mediated induction of CYP450 enzyme.	Hypertension [BA00-BA04]	[23]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Thiopental and Flibanserin.	Mood disorder [6A60-6E23]	[24]
Thalidomide	DM70BU5	Moderate	Additive CNS depression effects by the combination of Thiopental and Thalidomide.	Multiple myeloma [2A83]	[18]
Apraclonidine	DMO4PVE	Moderate	Additive CNS depression effects by the combination of Thiopental and Apraclonidine.	Optic nerve disorder [9C40]	[25]
Biperiden	DME78OA	Moderate	Additive CNS depression effects by the combination of Thiopental and Biperiden.	Parkinsonism [8A00]	[26]
Tizanidine	DMR2IQ4	Moderate	Additive CNS depression effects by the combination of Thiopental and Tizanidine.	Tonus and reflex abnormality [MB47]	[27]
Propafenone	DMPIBJK	Minor	Increased metabolism of Thiopental caused by Propafenone.	Ventricular tachyarrhythmia [BC71]	[28]
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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: 2579).
2	Thiopental FDA Label
3	BDDCS applied to over 900 drugs
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	EMC Summary of Product Characteristics: Thiopental powder for solution for injection
6	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
7	The general anesthetic propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. Br J Pharmacol. 2003 Jul;139(5):1005-13.
8	Lerman J. (2014). Neonatal Anesthesia. Springer.
9	Ketamine hypertension and the renin-angiotensin system. Clin Exp Hypertens A. 1983;5(6):875-83. doi: 10.3109/10641968309081814.
10	Thiopental-induced apoptosis in lymphocytes is independent of CD95 activation. Anesthesiology. 2005 Sep;103(3):576-84. doi: 10.1097/00000542-200509000-00021.
11	Thiopental protects human T lymphocytes from apoptosis in vitro via the expression of heat shock protein 70. J Pharmacol Exp Ther. 2008 Apr;325(1):217-25. doi: 10.1124/jpet.107.133108. Epub 2008 Jan 24.
12	Effects of different anaesthetic agents on immune cell function in vitro. Eur J Anaesthesiol. 2005 Aug;22(8):616-23. doi: 10.1017/s0265021505001031.
13	Thiopental inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappaB through suppression of kappaB kinase activity. Anesthesiology. 2003 Aug;99(2):360-7. doi: 10.1097/00000542-200308000-00017.
14	Gill SS, Wright EM, Reilly CS "Pharmacokinetic interaction of propofol and fentanyl: single bolus injection study." Br J Anaesth 65 (1990): 760-5. [PMID: 2265045]
15	Product Information. Lysodren (mitotane). Bristol-Myers Squibb, Princeton, NJ.
16	Hamann SR, Blouin RA, Chang SL, et al "Effects of hemodynamic changes on the elimination kinetics of verapamil and nifedipine." J Pharmacol Exp Ther 231 (1984): 301-5. [PMID: 6491984]
17	Bukowskyj M, Nakatsu K, Munt PW "Theophylline reassessed." Ann Intern Med 101 (1984): 63-73. [PMID: 6145380]
18	Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
19	Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5. [PMID: 5929537]
20	Product Information. Paxil (paroxetine). GlaxoSmithKline, Research Triangle Park, NC.
21	Cerner Multum, Inc. "Australian Product Information.".
22	Richter E, Breimer DD, Zilly W "Disposition of hexobarbital in intra- and extrahepatic cholestasis in man and the influence of drug metabolism-inducing agents." Eur J Clin Pharmacol 17 (1980): 197-202. [PMID: 7363932]
23	Rutledge DR, Pieper JA, Mirvis DM "Effects of chronic phenobarbital on verapamil dispostion in humans." J Pharmacol Exp Ther 246 (1988): 7-13. [PMID: 3392664]
24	Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
25	Product Information. Alphagan (brimonidine ophthalmic). Allergan Inc, Irvine, CA.
26	Product Information. Artane (trihexyphenidyl). Lederle Laboratories, Wayne, NJ.
27	Product Information. Zanaflex (tizanidine). Acorda Therapeutics, Hawthorne, NY.
28	Sams RA, Muir WW. Effects of phenobarbital on thiopental pharmacokinetics in greyhounds. Am J Vet Res. 1988;49(2):245-249. [PMID: 3348533]