HALOTHANE

Details

Stereochemistry	RACEMIC
Molecular Formula	C2HBrClF3
Molecular Weight	197.382
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)(F)C(Cl)Br

InChI

InChIKey=BCQZXOMGPXTTIC-UHFFFAOYSA-N

InChI=1S/C2HBrClF3/c3-1(4)2(5,6)7/h1H

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/pro/halothane.html

Halothane, USP is an inhalation anesthetic chemically designated 2-Bromo-2-chloro-1,1,1-trifluoroethane. Halothane, sold under the brand name Fluothane among others, is a general anesthetic. It can be used to start or maintain anesthesia. One of its benefits is that it does not increase the production of saliva which can be particularly useful in those who are difficult to intubate. Side effects include an irregular heartbeat, decreased effort to breath (respiratory depression), and liver problems. It should not be used in people with porphyria or a history of malignant hyperthermia either in themselves or their family members. It is unclear whether use during pregnancy is harmful to the baby, and it is not generally recommended for use during a cesarean section. Fluothane is no longer commercially available in the United States.

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/22836013	Positive Allosteric Modulator 179
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22836013	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.drugs.com/pro/halothane.html	Primary		Approved 8429	FLUOTHANE Approved Use INDICATIONS. Halothane is indicated for the induction and maintenance of general anesthesia. Launch Date -3.72643201E11

Doses

Dose	Population	Adverse events
4 % single, respiratory (min) Overdose Dose: 4 % Route: respiratory Route: single Dose: 4 % Sources: https://pubmed.ncbi.nlm.nih.gov/276284 Page: p.212	unhealthy, 3 n = 1 Health Status: unhealthy Condition: anesthesia for dental disorder Age Group: 3 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/276284 Page: p.212	Disc. AE: Change in ECG, Blood pressure systolic decreased... AEs leading to discontinuation/dose reduction: Change in ECG Blood pressure systolic decreased Sources: https://pubmed.ncbi.nlm.nih.gov/276284 Page: p.212

AEs

AE	Significance	Dose	Population
Blood pressure systolic decreased	Disc. AE	4 % single, respiratory (min) Overdose Dose: 4 % Route: respiratory Route: single Dose: 4 % Sources: https://pubmed.ncbi.nlm.nih.gov/276284 Page: p.212	unhealthy, 3 n = 1 Health Status: unhealthy Condition: anesthesia for dental disorder Age Group: 3 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/276284 Page: p.212
Change in ECG	Disc. AE	4 % single, respiratory (min) Overdose Dose: 4 % Route: respiratory Route: single Dose: 4 % Sources: https://pubmed.ncbi.nlm.nih.gov/276284 Page: p.212	unhealthy, 3 n = 1 Health Status: unhealthy Condition: anesthesia for dental disorder Age Group: 3 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/276284 Page: p.212

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 882	CYP2A6 543 CYP2E1 667 CYP2B6 664

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9212147/	yes		yes (co-administration study) Comment: plasma concentration of chlorzoxazone (substrate) increased 2.5-fold after 3 h of halothane inhalation in rabbits Sources: https://pubmed.ncbi.nlm.nih.gov/9212147/

Drug as victim

Target	Modality	Activity
CYP2A6 543	substrate 3367 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0950350198800299 Page: 12.0	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/14515060/ Page: 7.0	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 101.0	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 148.0	yes
CYP2E1 667	substrate 3367 Sources: https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.27253	yes
CYP3A4 1737	substrate 3367 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0950350198800299 Page: 12.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubs.asahq.org/anesthesiology/article/97/4/921/40485/Kinetic-Modulation-of-HERG-Potassium-Channels-by

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5615	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5615
ChemicalBook	CB8488628	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8488628
MolPort	MolPort-001-772-004	https://www.molport.com/shop/molecule-link/MolPort-001-772-004
eMolecules	484876	https://www.emolecules.com/cgi-bin/more?vid=484876

PubMed

Title	Date	PubMed
Use of structural alterations in the synthesis of halothane metabolite antigens to mimic halothane-induced immunogen.	1990	1703476
Severe bradycardia and sinus arrest after administration of vecuronium, fentanyl and halothane. A case report.	1991 Aug 17	1678901
Screening for antibodies associated with halothane hepatitis.	1991 Dec	1768541
Steal-prone coronary anatomy and myocardial ischemia associated with four primary anesthetic agents in humans.	1991 Jan	1824584
Is premedication with oral glycopyrrolate as effective as oral atropine in attenuating cardiovascular depression in infants receiving halothane for induction of anesthesia?	1991 Sep	1867419
Halothane hepatitis 28 years after primary exposure.	1992 Apr	1554130
Isoflurane does not increase the incidence of intraoperative myocardial ischaemia compared with halothane during vascular surgery.	1992 Dec	1467104
Molecular mimicry of trifluoroacetylated human liver protein adducts by constitutive proteins and immunochemical evidence for its impairment in halothane hepatitis.	1992 Dec 1	1459138
Nalidixic acid-induced hemolytic anemia complicating halothane-induced hepatitis.	1992 May	1597360
The calcium-binding protein calreticulin is covalently modified in rat liver by a reactive metabolite of the inhalation anesthetic halothane.	1992 May-Jun	1504264
Muscle rigidity following halothane anesthesia in two patients with Freeman-Sheldon syndrome.	1992 Sep	1519800
[Heart rhythm variability as a criterion for selecting anesthesia for maxillofacial surgical procedures in children].	2003	14671595
Calcium release from sarcoplasmic reticulum is facilitated in human myotubes derived from carriers of the ryanodine receptor type 1 mutations Ile2182Phe and Gly2375Ala.	2003 Fall	14641996
In vivo measurement of bending stiffness in fracture healing.	2003 Mar 28	14599296
[Halothane-induced hepatitis. 8 case reports].	2003 Nov	14986543
Biological activity of bacterial lectins and their molecular complexes with heterocyclic bis-adducts.	2003 Sep-Oct	14723158
Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo.	2004 Dec	15564938
Functional characterization of malignant hyperthermia-associated RyR1 mutations in exon 44, using the human myotube model.	2004 Jul	15210166
Development of a halothane-adrenaline arrhythmia model using in vivo Guinea pigs.	2004 Jun	15215648
Halothane induced hepatitis: case report.	2004 Oct	15715133
Gas-phase positive ion chemistry of 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) upon electron ionization within an ion trap mass spectrometer.	2005	15880636
Positive and negative ion chemistry of the anesthetic halothane (1-bromo-1-chloro-2,2,2-trifluoroethane) in air plasma at atmospheric pressure.	2005	15645512
Identification of the central imidazoline receptor subtype involved in modulation of halothane-epinephrine arrhythmias in rats.	2005 Dec	16301242
Fenamates and diltiazem modulate lipid-sensitive mechano-gated 2P domain K(+) channels.	2005 Dec	16075240
Reproducible loss of CA1 neurons following carotid artery occlusion combined with halothane-induced hypotension.	2005 Feb 8	15694917
Truncated human serum albumin retains general anaesthetic binding activity.	2005 May 15	15634193
Fulminant hepatic failure following halothane anaesthesia.	2005 Oct	16085447
The role of surfactant protein D in the colonisation of the respiratory tract and onset of bacteraemia during pneumococcal pneumonia.	2005 Oct 28	16255775
Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden.	2005 Sep	16165719
A guest molecule-host cavity fitting algorithm to mine PDB for small molecule targets.	2006 Aug	16904958
Functional hyperemic response in the rat visual cortex under halothane anesthesia.	2006 Feb 6	16256270
Putting theory into practice: James Black, receptor theory and the development of the beta-blockers at ICI, 1958-1978.	2006 Jan	16502872
Free radical theory of autoimmunity.	2006 Jun 7	16759382
Clinical observations surrounding an increased incidence of postanesthetic myopathy in halothane-anesthetized horses.	2006 Mar	16476002
Halothane induces oxidative stress and NF-kappaB activation in rat liver: protective effect of propofol.	2006 Oct 3	16965849
Switch from planktonic to sessile life: a major event in pneumococcal pathogenesis.	2006 Sep	16925554
Reduced cardiovascular reactivity to stress but not feeding in renin enhancer knockout mice.	2007 Aug	17679040
Halothane induced fulminant hepatic failure.	2007 Feb	17288858
The common chemical motifs within anesthetic binding sites.	2007 Feb	17242087
Therapeutic potential of neuronal two-pore domain potassium-channel modulators.	2007 Jul	17659475
Inhaled anesthetic modulation of amyloid beta(1-40) assembly and growth.	2007 Jul	17627480
Detrimental effects of halothane narcosis on damage after endothelin-1-induced MCAO.	2007 May 15	17197033
Transgenic upregulation of IK1 in the mouse heart is proarrhythmic.	2007 Sep	17546530
A novel approach to detect hot-spots in large-scale multivariate data.	2007 Sep 11	17848185
Inhalation anaesthesia: from diethyl ether to xenon.	2008	18175089
Stimulatory effect of Eucalyptus essential oil on innate cell-mediated immune response.	2008 Apr 18	18423004
Trifluoroacetylated IgG4 antibodies in a child with idiosyncratic acute liver failure after first exposure to halothane.	2008 Aug	18664874
Cardiomyocyte formation by skeletal muscle-derived multi-myogenic stem cells after transplantation into infarcted myocardium.	2008 Mar 12	18335059
Disruption of FAK signaling: a side mechanism in cytotoxicity.	2008 Mar 12	18215454
Interaction of anesthetics with the Rho GTPase regulator Rho GDP dissociation inhibitor.	2008 Sep 9	18702520

Patents

Sample Use Guides

In Vivo Use Guide

The induction dose varies from patient to patient. The maintenance dose varies from 0.5 to 1.5%. Halothane may be administered with either oxygen or a mixture of oxygen and nitrous oxide.

Route of Administration: Respiratory

In Vitro Use Guide

Mechanically dissociated rat hippocampal CA3 neurons was used for evaluation of halothane effects on synaptic and extrasynaptic GABAA and glutamate receptor responses. All receptor mediated currents were recorded in whole-cell patch recording under the voltage clamp condition at a holding potential of 0mV for GABAergic inhibitory postsynaptic currents or -65 mV for glutamatergic excitatory postsynaptic currents (EPSCs). Halothane solution (up to 20mM) was continuously applied to the isolated neuron by Y-tube system using silicon tubing directly connected to the glass test tube and all well sealed with parafilm to avoid any evaporation and loss of anesthetic.

Name

Type

Language

HALOTHANE

Official Name

English

HALOTHANE [HSDB]

Common Name

English

HALOTHANE [WHO-IP]

Common Name

English

HALOTHANE [USP MONOGRAPH]

Common Name

English

HALOTHANE [EP MONOGRAPH]

Common Name

English

NSC-143490

Code

English

HALOTHANE [ORANGE BOOK]

Common Name

English

2-Bromo-2-chloro-1,1,1-trifluoroethane

Common Name

English

HALOTHANE [EP IMPURITY]

Common Name

English

ETHANE, 2-BROMO-2-CHLORO-1,1,1-TRIFLUORO-,(±)-

Common Name

English

HALOTHANUM [WHO-IP LATIN]

Common Name

English

halothane [INN]

Common Name

English

Halothane [WHO-DD]

Common Name

English

FREON 123B1

Code

English

(±)-2-BROMO-2-CHLORO-1,1,1-TRIFLUOROETHANE

Systematic Name

English

FLUOTHANE

Brand Name

English

HALOTHANE [MI]

Common Name

English

HALOTHANE [VANDF]

Common Name

English

HALOTHANE [GREEN BOOK]

Common Name

English

HALOTHANE [JAN]

Common Name

English

HALOTHANE [MART.]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N01AB01