THIAMYLAL

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H18N2O2S
Molecular Weight	254.349
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=XLOMZPUITCYLMJ-UHFFFAOYSA-N

InChI=1S/C12H18N2O2S/c1-4-6-8(3)12(7-5-2)9(15)13-11(17)14-10(12)16/h5,8H,2,4,6-7H2,1,3H3,(H2,13,14,15,16,17)

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB01154 | http://www.minclinic.ru/drugs/drugs_eng/S/Surital.html

Thiamylal is a barbiturate that is administered intravenously for the production of complete anesthesia of short duration, for the induction of general anesthesia, or for inducing a hypnotic state. Thiamylal, a barbiturate, is used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia. Thiamylal 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	Potency
GABA-A receptor; anion channel 203 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11900777 \| https://www.drugbank.ca/drugs/DB01154 \| http://drugcentral.org/drugcard/2626	Positive Allosteric Modulator 186
Sulfonylurea receptor 2, Kir6.2 11 Target ID: CHEMBL2095198 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14739809	Inhibitor 8504	183.0 µM [EC50]
ATP-sensitive inward rectifier potassium channel 11 10 Target ID: Q14654 Gene ID: 3767.0 Gene Symbol: KCNJ11 Target Organism: Homo sapiens (Human) Sources: https://www.drugbank.ca/drugs/DB01154	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: http://www.minclinic.ru/drugs/drugs_eng/S/Surital.html	Primary		Approved 8583	Surital Approved Use Surital Indication: Used for the production of complete anesthesia of short duration, for the induction of general anesthesia, and for inducing a hypnotic state. Launch Date 1951

F_unbound

Value	Dose	Analyte	Population
6.7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10960410	9 μmol single, unknown dose: 9 μmol route of administration: UNKNOWN experiment type: SINGLE co-administered:	THIAMYLAL serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
7.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10960410	18 μmol single, unknown dose: 18 μmol route of administration: UNKNOWN experiment type: SINGLE co-administered:	THIAMYLAL serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10960410	90 μmol single, unknown dose: 90 μmol route of administration: UNKNOWN experiment type: SINGLE co-administered:	THIAMYLAL serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
25 mg/kg single, rectal Dose: 25 mg/kg Route: rectal Route: single Dose: 25 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7900578	healthy, 3 months - 12 years Health Status: healthy Age Group: 3 months - 12 years Sources: https://pubmed.ncbi.nlm.nih.gov/7900578	Other AEs: Anal irritation, Discharge... Other AEs: Anal irritation (58%) Discharge (58%) Sleepiness (14%) Nausea (15%) Vomiting (15%) Stumbling (13%) Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
10 mg/kg single, rectal Dose: 10 mg/kg Route: rectal Route: single Dose: 10 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/16368209	healthy, 3 years (range: 20 days–20 years) Health Status: healthy Age Group: 3 years (range: 20 days–20 years) Sources: https://pubmed.ncbi.nlm.nih.gov/16368209	Sources: https://pubmed.ncbi.nlm.nih.gov/16368209
9.3 mg/kg single, intravenous Highest studied dose Dose: 9.3 mg/kg Route: intravenous Route: single Dose: 9.3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/32359890	healthy, 31.5 months (range: 14.0–56.8 months) Health Status: healthy Age Group: 31.5 months (range: 14.0–56.8 months) Sources: https://pubmed.ncbi.nlm.nih.gov/32359890	Sources: https://pubmed.ncbi.nlm.nih.gov/32359890

AEs

AE	Significance	Dose	Population
Stumbling	13%	25 mg/kg single, rectal Dose: 25 mg/kg Route: rectal Route: single Dose: 25 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7900578	healthy, 3 months - 12 years Health Status: healthy Age Group: 3 months - 12 years Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Sleepiness	14%	25 mg/kg single, rectal Dose: 25 mg/kg Route: rectal Route: single Dose: 25 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7900578	healthy, 3 months - 12 years Health Status: healthy Age Group: 3 months - 12 years Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Nausea	15%	25 mg/kg single, rectal Dose: 25 mg/kg Route: rectal Route: single Dose: 25 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7900578	healthy, 3 months - 12 years Health Status: healthy Age Group: 3 months - 12 years Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Vomiting	15%	25 mg/kg single, rectal Dose: 25 mg/kg Route: rectal Route: single Dose: 25 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7900578	healthy, 3 months - 12 years Health Status: healthy Age Group: 3 months - 12 years Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Anal irritation	58%	25 mg/kg single, rectal Dose: 25 mg/kg Route: rectal Route: single Dose: 25 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7900578	healthy, 3 months - 12 years Health Status: healthy Age Group: 3 months - 12 years Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Discharge	58%	25 mg/kg single, rectal Dose: 25 mg/kg Route: rectal Route: single Dose: 25 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7900578	healthy, 3 months - 12 years Health Status: healthy Age Group: 3 months - 12 years Sources: https://pubmed.ncbi.nlm.nih.gov/7900578

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087 activator 150	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 1079 OATP1B3 961	CYP2E1 729

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	activator 342 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTIwMTA2NSJ9fQ%3D%3D	no [Activation >12.5893 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTIwMTA2NSJ9fQ%3D%3D	yes [Activation 12.5893 uM]
PXR 51	activator 342 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50103607, https://pubmed.ncbi.nlm.nih.gov/20966043/	yes [EC50 4.1 uM]
CYP3A4 2633	inducer 1966 Sources: https://go.drugbank.com/drugs/DB01154\| http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50103607\| https://pubmed.ncbi.nlm.nih.gov/20966043/	yes [EC50 6.4 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyMDEwNjUifX0%3D, https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyMDEwNjUifX0%3D, https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity
CYP2C9 1193	substrate 4014 Sources: https://go.drugbank.com/drugs/DB01154, https://pubmed.ncbi.nlm.nih.gov/10960410/	major
CYP2E1 729	substrate 4014 Sources: https://go.drugbank.com/drugs/DB01154, https://pubmed.ncbi.nlm.nih.gov/10960410/	minor
CYP3A4 1946	substrate 4014 Sources: https://go.drugbank.com/drugs/DB01154, https://pubmed.ncbi.nlm.nih.gov/10960410/	minor

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9536	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9536
eMolecules	595235	https://www.emolecules.com/cgi-bin/more?vid=595235

PubMed

Title	Date	PubMed
A hypotensive episode caused by amitriptyline?	1969 Oct 4	4186181
Lack of compensatory increase in plasma free-norepinephrine during hypotension induced by intravenous thiamylal anesthesia.	1973 Jul	4730132
Arrhythmias in dogs associated with epinephrine and thiamylal anesthesia.	1975 Sep	51600
Arrhythmogenic properties of thiamylal sodium in the dog.	1976 Jan 15	54351
Hypertension in bulls and steers anesthetized with guaifenesin-thiobarbiturate-halothane combination.	1986 Jul	3740628
Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog.	1991 Oct	1897763
Propofol versus thiamylal-enflurane anesthesia for outpatient laparoscopy.	1992 May-Jun	1535202
[A case of adult Reye's syndrome with favorable outcome despite status epilepticus].	1996 Nov	9046859
Effects of volatile and intravenous anesthetics on the uptake of GABA, glutamate and dopamine by their transporters heterologously expressed in COS cells and in rat brain synaptosomes.	2001 Aug 6	11514107
[Stump pain relieved by continuous intravenous ketamine infusion therapy].	2001 Jul	11510069
Values of the bispectral index do not parallel the hemodynamic response to the rapid increase in isoflurane concentration.	2001 Nov	11698313
[Anesthetic management of a patient with Dyggve-Melchior-Clausen syndrome].	2001 Oct	11712346
[Anesthesia for electroconvulsive therapy during pregnancy--a case report].	2001 Sep	11593722
Tracheal lidocaine attenuates the cardiovascular response to endotracheal intubation.	2001 Sep	11546711
Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans.	2002 Apr	11940752
A study of the in vitro clinical interaction between lidocaine and premedications using rat liver microsomes.	2002 Aug	12412639
[Anesthetic management of a patient with dentato-rubro-pallido-luysian atrophy].	2002 Aug	12229143
[Anesthetic management for elective cesarean section due to placenta previa in a patient with moyamoya disease].	2002 Dec	12607271
Effects of thiamylal, sevoflurane and isoflurane on the cortically recorded somatosensory evoked potentials.	2002 Dec	12510912
Anesthetic management for a patient with Jansky-Bielschowsky disease.	2002 Jan	11782333
Perioperative factors associated with puppy vigor after delivery by cesarean section.	2002 Jan-Feb	11804323
["Cannot-ventilate" after anesthetic induction in a patient with rapidly increased laryngeal tumor].	2002 Jul	12166285
[Quantitative analysis of plasma concentration of barbiturate for diagnosis of brain death].	2002 Jun	12094685
Electroconvulsive therapy with thiamylal or propofol during pregnancy.	2002 Mar	11861360
The bispectral index response to tracheal intubation is similar in normotensive and hypertensive patients.	2002 May	11983658
Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice.	2002 May	11900777
[Anesthetic management of a patient with Evans syndrome--benefit of perioperative hemodilutional autologous blood transfusion].	2002 Nov	12481456
Barbiturates induce mitochondrial depolarization and potentiate excitotoxic neuronal death.	2002 Nov 1	12417645
Effects of barbiturates on human platelet aggregation differ depending on their chemical structures.	2003 Aug	12897810
Intravenous nicorandil prevents thiamylal-fentanyl-induced bronchoconstriction in humans.	2003 Feb	12576956
The ED(95) of end-tidal sevoflurane concentration for the smooth exchange of the tracheal tube for a laryngeal mask airway is 2.97%.	2003 Feb	12560312
Effects of the intravenously administered anaesthetics ketamine, propofol, and thiamylal on the cortical renal blood flow in rats.	2003 May	12660475
Thiamylal and pentobarbital have opposite effects on human platelet aggregation in vitro.	2003 Nov	14570651
Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels.	2004 Feb	14739809
[Complete neurological recovery in a patient with decerebrate rigidity following cardiac arrest from acute airway obstruction by advanced laryngeal cancer].	2004 Mar	15071883
[Case of premature ventricular contraction immediately after electroconvulsive therapy in a depressive patient].	2005 Jan	15717468
Efficacy and adverse effects of rectal thiamylal with oral triclofos for children undergoing magnetic resonance imaging.	2006 Apr	16368209
Utility of the auditory evoked potentials index as an indicator for endotracheal intubation.	2006 Dec	17233364
Effects of premedication medicines on the formation of the CYP3A4-dependent metabolite of ropivacaine, 2', 6'-Pipecoloxylidide, on human liver microsomes in vitro.	2006 Feb	16445592
Lethal injection for execution: chemical asphyxiation?	2007 Apr	17455994
[Airway access using an endotracheal tube changer for safe extubation in an infant with a difficult airway].	2008 Feb	18277563
Anaesthesia for in vitro fertilisation.	2009 Aug	20640202
[Anesthetic management for a patient with significant orthostatic hypotension probably due to pure autonomic failure].	2009 Aug	19702221
[Case report of dentatorubral pallidoluysian atrophy in a patient on a ketogenic diet].	2009 Jun	19522273
Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?	2009 Oct 27	19860902
The intravenous anesthetics barbiturates inhibit hypoxia-inducible factor 1 activation.	2009 Sep 1	19595685
Effects of propofol on beta-adrenoceptor-mediated signal transduction in cardiac muscle; role of cAMP.	2010 Apr	20508795
Intravenous thiamylal and local anesthetic infiltration for pediatric facial repair procedures performed in emergency departments.	2010 Apr	20434100
Electromyographic study of differential sensitivity to succinylcholine of the diaphragm, laryngeal and somatic muscles: a swine model.	2010 Dec	21186012
A comparison of the effect on QT interval between thiamylal and propofol during anaesthetic induction*.	2010 Jul	20528837

Patents

Sample Use Guides

In Vivo Use Guide

In human medicine, thiamylal is used by the intravenous route as a 2.5% solution at an average dose ranging from 1 to 10 mg/kg bw.

Route of Administration: Intravenous

In Vitro Use Guide

In helical strips of dog cerebral, coronary, mesenteric, renal, and femoral arteries, the addition of thiamylal and thiopental, 10(-5) to 10(-3) M, caused a dose-related contraction.The persistent contraction was potentiated by 10(-4) M thiamylal but abolished at 10(-3) M. In the mesenteric artery soaked in Ca++-free media, the addition of Ca++ produced only a slight contraction, which was potentiated by thiamylal (10(-4) and 10(-3) M).

Name

Type

Language

THIAMYLAL

Common Name

English

NSC-120815

Preferred Name

English

THIAMYLAL [MI]

Common Name

English

THIAMYLAL [VANDF]

Common Name

English

Thiamylal [WHO-DD]

Common Name

English

5-Allyl-5-(1-methylbutyl)-2-thiobarbituric acid

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67084