THIAMYLAL SODIUM

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H17N2O2S.Na
Molecular Weight	276.33
Optical Activity	( + / - )
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=LYZGJWXNOGIVQA-UHFFFAOYSA-M

InChI=1S/C12H18N2O2S.Na/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);/q;+1/p-1

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 197 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 178
Sulfonylurea receptor 2, Kir6.2 11 Target ID: CHEMBL2095198 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14739809	Inhibitor 8146	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 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 607 Sources: http://www.minclinic.ru/drugs/drugs_eng/S/Surital.html	Primary		Approved 8307	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 -5.99616E11

F_unbound

Value	Dose	Analyte	Population
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
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
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 (starting) 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 n = 462 Health Status: healthy Age Group: 3 months - 12 years Population Size: 462 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 Co-administed with:: triclofos(80–100 mg/kg, orally) 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 (starting) 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 n = 462 Health Status: healthy Age Group: 3 months - 12 years Population Size: 462 Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Sleepiness	14%	25 mg/kg single, rectal (starting) 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 n = 462 Health Status: healthy Age Group: 3 months - 12 years Population Size: 462 Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Nausea	15%	25 mg/kg single, rectal (starting) 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 n = 462 Health Status: healthy Age Group: 3 months - 12 years Population Size: 462 Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Vomiting	15%	25 mg/kg single, rectal (starting) 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 n = 462 Health Status: healthy Age Group: 3 months - 12 years Population Size: 462 Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Anal irritation	58%	25 mg/kg single, rectal (starting) 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 n = 462 Health Status: healthy Age Group: 3 months - 12 years Population Size: 462 Sources: https://pubmed.ncbi.nlm.nih.gov/7900578
Discharge	58%	25 mg/kg single, rectal (starting) 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 n = 462 Health Status: healthy Age Group: 3 months - 12 years Population Size: 462 Sources: https://pubmed.ncbi.nlm.nih.gov/7900578

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670 inhibitor 1532 inducer 753 activator 77	substrate 985

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 770 OATP1B3 691	CYP2E1 633

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1857	activator 208 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTIwMTA2NSJ9fQ%3D%3D	no [Activation >12.5893 uM]
CYP3A4 1857	inhibitor 3185 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTIwMTA2NSJ9fQ%3D%3D	yes [Activation 12.5893 uM]
PXR 45	activator 208 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 1857	inducer 1515 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 785	inhibitor 3185 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 700	inhibitor 3185 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 985	substrate 3264 Sources: https://go.drugbank.com/drugs/DB01154, https://pubmed.ncbi.nlm.nih.gov/10960410/	major
CYP2E1 633	substrate 3264 Sources: https://go.drugbank.com/drugs/DB01154, https://pubmed.ncbi.nlm.nih.gov/10960410/	minor
CYP3A4 1670	substrate 3264 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
Arrhythmogenic properties of thiamylal sodium in the dog.	1976 Jan 15	54351
Propofol versus thiamylal-enflurane anesthesia for outpatient laparoscopy.	1992 May-Jun	1535202
[A case of ventricular tachycardia immediately after electroconvulsive therapy in a schinzophrenic patient].	2001 Jan	11211751
Values of the bispectral index do not parallel the hemodynamic response to the rapid increase in isoflurane concentration.	2001 Nov	11698313
Tracheal lidocaine attenuates the cardiovascular response to endotracheal intubation.	2001 Sep	11546711
[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
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
[Propofol was useful for intractable convulsion in a patient with tetanus: a case report].	2003 Feb	12649877
[Anesthetic management for cesarean section in a patient with corrected transposition of great arteries].	2004 Nov	15587180
Premedication medicines do not cause drug metabolic interaction with propofol using human liver microsomes in vitro.	2004 Oct	15351923
A study of the in vitro interaction between lidocaine and premedications using human liver microsomes.	2005 Apr	15811173
[Pressor responses to inhalation of isoflurane during induction of anesthesia and subsequent tracheal intubation].	2005 Aug	16104539
[Anesthetic management in a patient with Goldenhar's syndrome using a perilaryngeal airway and a videolaryngoscope].	2005 Dec	16370341
[A survival case of tetanus complicated with disseminated intravascular coagulation syndrome in the elderly, rescued by mechanical ventilation and administration of thiamylal].	2005 Jan	15717480
[Nitroglycerin to relax the uterus during cesarean delivery for the low birthweight baby].	2005 Mar	15794106
[Airway access using an endotracheal tube changer for safe extubation in an infant with a difficult airway].	2008 Feb	18277563
Immediate impact of electroconvulsive therapy on cardiac autonomic function in schizophrenia: a preliminary study.	2008 Mar	18060743
[Anesthetic management of the ex-utero intrapartum treatment (EXIT) procedure for giant epignathus and of the tumor excision].	2008 Oct	18975539
Anaesthesia for in vitro fertilisation.	2009 Aug	20640202
Thiamylal antagonizes the inhibitory effects of dorsal column stimulation on dorsal horn activities in humans.	2009 Aug	19393696
Thiamylal and thiopental attenuate beta-adrenergic signaling pathway by suppressing adenylyl cyclase in rat ventricular myocytes.	2009 Mar	19400552
Effects of propofol on beta-adrenoceptor-mediated signal transduction in cardiac muscle; role of cAMP.	2010 Apr	20508795
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 SODIUM

Common Name

English

4,6-(1H,5H)-PYRIMIDINEDIONE, DIHYDRO-5-(1-METHYLBUTYL)-5-(2-PROPENYL)-2-THIOXO-, MONOSODIUM SALT

Common Name

English

THIAMYLAL SODIUM [MART.]

Common Name

English

SURITAL

Brand Name

English

THIAMYLAL SODIUM [GREEN BOOK]

Common Name

English

NSC-759558

Code

English

SODIUM THIAMYLAL

Common Name

English

THIAMYLAL SODIUM [ORANGE BOOK]

Common Name

English

Sodium 5-allyl-5-(1-methylbutyl)-2-thiobarbiturate

Systematic Name

English

THIAMYLAL SODIUM SALT [MI]

Common Name

English

THIAMYLAL SODIUM [VANDF]

Common Name

English

THIAMYLAL SODIUM SALT

Common Name

English

Thiamylal sodium [WHO-DD]

Common Name

English

THIAMYLAL SODIUM [JAN]

Common Name

English

Classification Tree Code System Code

DEA NO.

2100