THIOPENTAL

US Previously Marketed

First marketed in 1934

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H18N2O2S
Molecular Weight	242.338
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC(C)C1(CC)C(=O)NC(=S)NC1=O

InChI

InChIKey=IUJDSEJGGMCXSG-UHFFFAOYSA-N

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)

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 197 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18619475	Positive Allosteric Modulator 178

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 607 Sources: https://www.medicines.org.uk/emc/medicine/14338	Palliative		Approved 8307	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
Local anesthetic-induced convulsions in man--an electroencephalographic study.	1966 Sep-Oct	5950380
A comparison of propaniid and thiopentone as induction agents for electro-convulsive therapy.	1969 Jun	5792883
Case reports: thiopentone anaphylaxis.	1972 Aug	4654818
Thrombophlebitis following thiopentone injection.	1972 Nov	4635835
Adverse reactions following fazadinium-thiopentone induction.	1979 Jul-Aug	42323
Venous complications after intravenous injection of diazepam, flunitrazepam, thiopentone and etomidate.	1980 Jun	6108669
Ketamine hypertension and the renin-angiotensin system.	1983	6349867
Domperidone--an acute dystonic reaction.	1985 Feb	3977040
Thiopental-related immune hemolytic anemia and renal failure. Specific involvement of red-cell antigen I.	1985 Feb 7	3969087
[Use of thiopental in man. Determination of this drug and its metabolites in plasma and urine by liquid phase chromatography and mass spectrometry].	1986	3093002
Asystole associated with vecuronium.	1986 Aug	2873831
Drug-induced arterial spasm relieved by lidocaine. Case report.	1986 Nov	3564823
Comparison of the induction characteristics of thiopentone and propofol in children.	1987 Nov	3500735
GABA involvement in naloxone induced reversal of respiratory paralysis produced by thiopental.	1988	2893236
Factors that influence cutaneous reactions following administration of thiopentone and atracurium.	1988 Oct	2974255
Thiopental infusion in the treatment of intracranial hypertension complicating fulminant hepatic failure.	1989 Sep	2759548
Evaluation of mast cell activation (tryptase) in two patients suffering from drug-induced hypotensoid reactions.	1991 May	1897443
The effects of thiopental sodium on fentanyl-induced muscle rigidity in a human model.	1991 Sep-Oct	1931065
Complications and side effects during thiopentone therapy in patients with severe head injuries.	1992 May	1595344
The influence of the timing of administration of thiopentone sodium on nitric oxide-mediated neurotoxicity in vitro.	2000 Mar 1	10704975
Effect of propofol at two injection rates or thiopentone on post-intubation apnoea in the dog.	2001 Feb	11263701
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
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
Thiopental inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappaB through suppression of kappaB kinase activity.	2003 Aug	12883408
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
Intermediates of Krebs cycle correct the depression of the whole body oxygen consumption and lethal cooling in barbiturate poisoning in rat.	2004 Oct 1	15337580
The effect of pretreatment with thiopental on reducing pain induced by rocuronium injection.	2005 Dec 31	16385651
Severe refractory status epilepticus owing to presumed encephalitis.	2005 Mar	15832606
Inhibitory effect of thiopental on ultra-rapid delayed rectifier K+ current in H9c2 cells.	2005 Oct	16217144
Intravenous propofol precipitates the hypotension induced by inadvertent epidural thiopental injection.	2006 Dec	17233371
Succinate and artificial maintenance of normal body temperature synergistically correct lethal disorders in thiopental coma rat.	2006 Jan 20	16242831
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
Thiopental pharmacokinetics in newborn infants: a case report of overdose.	2009 Oct	19583708
[Use of midazolam for refractory status epilepticus in children].	2010 Jun-Jul	20171707
Pretreatment with dexmedetomidine or thiopental decreases myoclonus after etomidate: a randomized, double-blind controlled trial.	2010 Mar	20018300

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

Common Name

English

THIOPENTAL [VANDF]

Common Name

English

THIOPENTAL CIII

Common Name

English

Thiopental [WHO-DD]

Common Name

English

THIOPENTAL CIII [USP-RS]

Common Name

English

THIOPENTAL [HSDB]

Common Name

English

Classification Tree Code System Code

LIVERTOX

953