THIOPENTAL SODIUM

First marketed in 1934

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H17N2O2S.Na
Molecular Weight	264.32
Optical Activity	( + / - )
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CCCC(C)C1(CC)C(=O)NC(=S)[N-]C1=O

InChI

InChIKey=AWLILQARPMWUHA-UHFFFAOYSA-M

InChI=1S/C11H18N2O2S.Na/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);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: https://www.medicines.org.uk/emc/medicine/14338 | http://www.spiegel.de/international/europe/death-penalty-opposition-eu-set-to-ban-export-of-drug-used-in-us-executions-a-803238.html |

Sodium thiopental (also known as Sodium Pentothal, thiopental) was discovered in 1930s by investigators working for Abbott Laboratories. Thiopental sodium was used for the induction of general anesthesia and is used as an adjunct to provide hypnosis during balanced anesthesia with other anesthetic agents, including analgesics and muscle relaxants. Thiopental sodium was also used as an adjunct for control of convulsive disorders of various etiology, including those caused by local anesthetics. Finally, thiopental sodium had been used to reduce the intracranial pressure in patients with increased intracranial pressure, if controlled ventilation is provided. Nevertheless, these prescriptions of drug were discontinued. In addition, this drug was banned for use in US executions. Thiopental sodium acts through the CNS with particular activity in the mesencephalic reticular activating system. It was shown, that mechanism of action of sodium thiopental via GABAA receptor. Thiopental binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 202 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18619475	Positive Allosteric Modulator 179

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.medicines.org.uk/emc/medicine/14338	Palliative		Approved 8429	PENTOTHAL Approved Use Pentothal (Thiopental Sodium for Injection) is indicated (1) as the sole anesthetic agent for brief (15 minute) procedures, (2) for induction of anesthesia prior to administration of other anesthetic agents, (3) to supplement regional anesthesia, (4) to provide hypnosis during balanced anesthesia with other agents for analgesia or muscle relaxation, (5) for the control of convulsive states during or following inhalation anesthesia, local anesthesia, or other causes, (6) in neurosurgical patients with increased intracranial pressure, if adequate ventilation is provided, and (7) for narcoanalysis and narcosynthesis in psychiatric disorders.

Doses

Dose	Population	Adverse events
500 mg multiple, intravenous (starting) Dose: 500 mg Route: intravenous Route: multiple Dose: 500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2759548	unhealthy, 31 years (range: 19 -44 years) n = 13 Health Status: unhealthy Age Group: 31 years (range: 19 -44 years) Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/2759548	Other AEs: Hypothermia... Other AEs: Hypothermia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/2759548

AEs

AE	Significance	Dose	Population
Hypothermia	1 patient	500 mg multiple, intravenous (starting) Dose: 500 mg Route: intravenous Route: multiple Dose: 500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2759548	unhealthy, 31 years (range: 19 -44 years) n = 13 Health Status: unhealthy Age Group: 31 years (range: 19 -44 years) Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/2759548

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:102166	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:102166
ChemicalBook	CB5265910	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5265910
eMolecules	594613	https://www.emolecules.com/cgi-bin/more?vid=594613

PubMed

Title	Date	PubMed
Metabolism of thiopental-S35 and thiopental-2-C14 by a rat liver mince and identification of pentobarbital as a major metabolite.	1955 Jul	13243246
Local anesthetic-induced convulsions in man--an electroencephalographic study.	1966 Sep-Oct	5950380
Further investigation into local complications of thiopentone injection.	1971 May	5556860
Abdominal-muscle rigidity induced by morphine and nitrous oxide.	1973 Apr	4350546
Thiopentone anaphylaxis--case report.	1975 Aug	1166949
Postischemic brain oxygenation with barbiturate therapy in rats.	1979 Aug	37043
Adverse reactions following fazadinium-thiopentone induction.	1979 Jul-Aug	42323
Brain blood flow and metabolism after global ischemia and post-insult thiopental therapy in monkeys.	1979 Sep-Oct	116395
Ketamine hypertension and the renin-angiotensin system.	1983	6349867
The safety of etomidate: a new intravenous anaesthetic induction agent.	1983 Jun	6322557
Another case of grand mal seizure after fentanyl administration.	1984 Apr	6422799
Domperidone--an acute dystonic reaction.	1985 Feb	3977040
[Phlebitis of the arm caused by pentothal infusion].	1985 Oct-Dec	4095143
Etomidate versus thiopental for induction of anesthesia.	1985 Sep	4025853
Asystole associated with vecuronium.	1986 Aug	2873831
Drug-induced arterial spasm relieved by lidocaine. Case report.	1986 Nov	3564823
Factors that influence cutaneous reactions following administration of thiopentone and atracurium.	1988 Oct	2974255
Acute macular neuroretinopathy following intravenous sympathomimetics.	1989	2629043
[Muscular rigidity caused by alfentanil: prevention].	1989 Jun	2575721
Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs: VII. Verapamil and thiopental.	1989 Oct	2802216
Thiopental infusion in the treatment of intracranial hypertension complicating fulminant hepatic failure.	1989 Sep	2759548
Intravenous midazolam significantly enhances the lethal effect of thiopental but not that of ketamine in mice.	2001 Dec	11735358
Dual effects of melatonin on barbiturate-induced narcosis in rats.	2001 Mar 16	11226639
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Effect of thiopental, propofol, and etomidate on vincristine toxicity in PC12 cells.	2002	11991087
Interaction of intravenous anesthetics with recombinant human M1-M3 muscarinic receptors expressed in chinese hamster ovary cells.	2002 Dec	12456425
Torsade de pointes and sudden death induced by thiopental and isoflurane anesthesia in dogs with cardiac electrical remodeling.	2002 Jan	12000977
Life-threatening hyperkalaemia following therapeutic barbiturate coma.	2002 Sep	12209290
Effect of sodium succinate on gas exchange in rats with barbiturate-induced coma.	2003 Apr	12910308
Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: A report of two cases.	2003 Mar-Apr	12677626
Seventy-four defibrillations for sotalol-induced torsades de pointes.	2004 Jul-Aug	15586745
Effects of different anaesthetic agents on immune cell function in vitro.	2005 Aug	16119599
Propofol and thiopental for refractory status epilepticus in children.	2005 Aug 23	16116121
Intravenous propofol precipitates the hypotension induced by inadvertent epidural thiopental injection.	2006 Dec	17233371
Synergism of isothermal regimen and sodium succinate in experimental therapy of barbiturate coma.	2006 Jul	17369903
Fulminant hyperammonaemia induced by thiopental coma in rats.	2006 Jul 25	16704891
Glutamate binding is altered in hippocampus and cortex of Wistar rats after pilocarpine-induced Status Epilepticus.	2007 Aug 31	17709190
Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits.	2007 Sep	17721245
Thiopental protects human T lymphocytes from apoptosis in vitro via the expression of heat shock protein 70.	2008 Apr	18218830
Thiopental pharmacokinetics in newborn infants: a case report of overdose.	2009 Oct	19583708
Incidence of postoperative delirium is high even in a population without known risk factors.	2014 Apr	24068571

Patents

Sample Use Guides

In Vivo Use Guide

Thiopental Sodium 500 mg Injection is administered intravenously normally as a 2.5% w/v (500 mg in 20 ml) solution. On occasions it may be administered as a 5% w/v solution (500 mg in 10 ml). The intravenous injection preparation should be used after reconstitution of the sterile powder with Water for Injections, usually to produce a 2.5% w/v solution and this should be discarded after seven hours.

Route of Administration: Intravenous

In Vitro Use Guide

In cultured spinal cord slices from mice, thiopental reduced action potential activity with an EC50 of 16.6 ± 2.4 μM. Recordings of GABAA and glycine receptor-mediated inhibitory currents indicated that the effect was largely mediated by GABAA receptors and that glycine receptors were not relevant targets. Specifically, 20 μM thiopental prolonged the decay time of spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) more than twofold. Although this prolongation of decay time increased the inhibitory charge per sIPSC the concomitant strong reduction of sIPSC frequency resulted in less inhibitory current entering the neurons via this route. However, 20 μM thiopental also induced a tonic current of 30 ± 10 pA, mediated by GABAA receptors; 50 μM thiopental nearly abolished sIPSC activity but augmented tonic currents to 69 ± 14 pA.

Name

Type

Language

THIOPENTAL SODIUM

Official Name

English

TRAPANAL

Brand Name

English

4,6(1H,5H)-PYRIMIDINEDIONE, 5-ETHYLDIHYDRO-5-(1-METHYLBUTYL)-2-THIOXO-, MONOSODIUM SALT, (±)-

Common Name

English

RAVONAL

Common Name

English

NESDONAL

Common Name

English

NSC-759557

Code

English

THIOPENTOBARBITONE SODIUM

Common Name

English

THIOPENTONE

Common Name

English

THIOPENTAL SODIUM [VANDF]

Common Name

English

THIOPENTAL SODIUM [MART.]

Common Name

English

PENTHIOBARBITAL SODIUM

Common Name

English

THIOPENTAL SODIUM [MI]

Common Name

English

THIOPENTAL SODIUM [ORANGE BOOK]

Common Name

English

Thiopental sodium [WHO-DD]

Common Name

English

SODIUM THIOPENTAL

Common Name

English

THIOPENTONE SODIUM

Common Name

English

PENTOTHAL

Brand Name

English

THIOPENTAL SODIUM [GREEN BOOK]

Common Name

English

SODIUM (±)-5-ETHYL-5-(1-METHYLBUTYL)-2-THIOBARBITURATE

Systematic Name

English

SODIUM PENTOTHAL

Brand Name

English

FARMOTAL

Common Name

English

thiopental sodium [INN]

Common Name

English

THIOPENTALUM NATRICUM [WHO-IP LATIN]

Common Name

English

THIOMEBUMAL SODIUM

Common Name

English

THIOPENTAL SODIUM [WHO-IP]

Common Name

English

THIOPENTAL SODIUM [USP MONOGRAPH]

Common Name

English

THIOPENTAL SODIUM [JAN]

Common Name

English

LEOPENTAL

Common Name

English

HYPNOSTAN

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67084