THIAMYLAL

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H18N2O2S
Molecular Weight	254.3501
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC(C)C1(CC=C)C(=NC(=S)N=C1O)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 109 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 80
Sulfonylurea receptor 2, Kir6.2 6 Target ID: CHEMBL2095198 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14739809	Inhibitor 3315	183.0 µM [EC50]
ATP-sensitive inward rectifier potassium channel 11 6 Target ID: Q14654 Gene ID: 3767.0 Gene Symbol: KCNJ11 Target Organism: Homo sapiens (Human) Sources: https://www.drugbank.ca/drugs/DB01154	Inhibitor 3315

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 260 Sources: http://www.minclinic.ru/drugs/drugs_eng/S/Surital.html	Primary		Approved 4033	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 882 inhibitor 753 inducer 374 activator 39	substrate 530

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 369 OATP1B3 319	CYP2E1 332

Drug as perpetrator

Target	Modality	Activity
CYP3A4 920	activator 106 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTIwMTA2NSJ9fQ%3D%3D	no [Activation >12.5893 uM]
CYP3A4 920	inhibitor 1612 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTIwMTA2NSJ9fQ%3D%3D	yes [Activation 12.5893 uM]
PXR 21	activator 106 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 920	inducer 772 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 379	inhibitor 1612 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 326	inhibitor 1612 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 530	substrate 1689 Sources: https://go.drugbank.com/drugs/DB01154, https://pubmed.ncbi.nlm.nih.gov/10960410/	major
CYP2E1 332	substrate 1689 Sources: https://go.drugbank.com/drugs/DB01154, https://pubmed.ncbi.nlm.nih.gov/10960410/	minor
CYP3A4 882	substrate 1689 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
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
Effects of thiamylal, sevoflurane and isoflurane on the cortically recorded somatosensory evoked potentials.	2002 Dec	12510912
[Anesthetic management of a patient with Evans syndrome--benefit of perioperative hemodilutional autologous blood transfusion].	2002 Nov	12481456
Hemodynamic and bispectral index responses to tracheal intubation during isoflurane or sevoflurane anesthesia.	2003	14625708
[Propofol was useful for intractable convulsion in a patient with tetanus: a case report].	2003 Feb	12649877
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
Effects of propofol on endotoxin-induced acute lung injury in rabbit.	2004 Feb	14966342
Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels.	2004 Feb	14739809
[Lockjaw caused by induction of anesthesia in a volunteer bone marrow donor].	2004 Mar	15071886
Premedication medicines do not cause drug metabolic interaction with propofol using human liver microsomes in vitro.	2004 Oct	15351923
[Effects of propofol and thiamylal on nicorandil induced ATP-sensitive potassium channel activities in cultured rat aortic smooth muscle cells].	2005 Apr	15852621
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
In vivo interaction of pulmonary intravascular macrophages with activated platelets in microvessels of equine lung after multiple exposures to halothane, isoflurane, and thiamylal: a comparative ultrastructural and cytochemical study.	2005 Jun	15880489
Deep sedation with methohexital or thiamylal with midazolam for invasive procedures in children with acute lymphoblastic leukemia.	2005 Sep-Oct	16640004
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
[Reduction of the concentration of isoflurane prevents tachycardia and hypertension associated with tracheal intubation].	2006 May	16715914
Effect of prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation.	2006 May	16531446
[Awareness during anesthesia with sevoflurane: a case report].	2006 Oct	17051987
[A boy with nystagmus, refractory dystonia and apneic attack due to alternating hemiplegia of childhood].	2007 Jul	17633086
[Clinical usefulness of remifentanil].	2007 Nov	18027598
Unilateral fixed dilated pupil during plastic surgery--a case report.	2007 Sep	17972621
[Case of general anesthesia combined with epidural anesthesia in a pregnant woman undergoing thoracotomy for spontaneous pneumothorax].	2008 Feb	18277570
[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
[Grand mal convulsion after an interscalene block with ropivacaine].	2009 Apr	19364012
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
Thiamylal antagonizes the inhibitory effects of dorsal column stimulation on dorsal horn activities in humans.	2009 Aug	19393696
[Case report of dentatorubral pallidoluysian atrophy in a patient on a ketogenic diet].	2009 Jun	19522273
Thiamylal and thiopental attenuate beta-adrenergic signaling pathway by suppressing adenylyl cyclase in rat ventricular myocytes.	2009 Mar	19400552
[Hypertension with tachycardia caused by propofol during induction of general anesthesia].	2009 May	19462811
[General anesthesia for cesarean section in a patient with moyamoya disease].	2009 May	19462810
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

THIAMYLAL [MI]

Common Name

English

THIAMYLAL [VANDF]

Common Name

English

NSC-120815

Code

English

THIAMYLAL [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67084