METHOHEXITAL SODIUM

Details

Stereochemistry	MIXED
Molecular Formula	C14H17N2O3.Na
Molecular Weight	284.2861
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CCC#CC(C)C1(CC=C)C(=O)[N-]C(=O)N(C)C1=O

InChI

InChIKey=KDXZREBVGAGZHS-UHFFFAOYSA-M

InChI=1S/C14H18N2O3.Na/c1-5-7-8-10(3)14(9-6-2)11(17)15-13(19)16(4)12(14)18;/h6,10H,2,5,9H2,1,3-4H3,(H,15,17,19);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/011559s041lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/1842156

Methohexital is an ultrashort-acting barbiturate widely used in dentistry because of its rapid onset, predictable effects, and short duration of action. It was marked under the name brevital sodium for the intravenous anaesthesia. It has also been commonly used to induce deep sedation. Like other barbiturates, methohexital exerts its effects through the gamma-aminobutyric acid (GABA) receptor complex. By binding to its own receptor on the complex, methohexital augments the inhibitory effect of GABA on neurons and additionally can exert a similar effect independent of GABA.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 203 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1842156	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/011559s041lbl.pdf	Preventing		Approved 8583	BREVITAL SODIUM Approved Use Brevital Sodium can be used in adults as follows: For intravenous induction of anesthesia prior to the use of other general anesthetic agents. For intravenous induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for short surgical procedures; Brevital Sodium may be given by infusion or intermittent injection. For use along with other parenteral agents, usually narcotic analgesics, to supplement subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for longer surgical procedures. As intravenous anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli (see WARNINGS ). As an agent for inducing a hypnotic state. Brevital Sodium can be used in pediatric patients older than 1 month as follows: For rectal or intramuscular induction of anesthesia prior to the use of other general anesthetic agents. For rectal or intramuscular induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents for short surgical procedures. As rectal or intramuscular anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Launch Date 1960

C_max

Value	Dose	Co-administered	Analyte	Population
2.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4005094	25 mg/kg single, rectal dose: 25 mg/kg route of administration: Rectal experiment type: SINGLE co-administered:		METHOHEXITAL plasma	Homo sapiens population: HEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
2.39 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2024566	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	METHOHEXITAL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.24 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2024566/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	METHOHEXITAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.71 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2024566/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	METHOHEXITAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
151 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2024566	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	METHOHEXITAL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
136 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2024566/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	METHOHEXITAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
204 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2024566/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	METHOHEXITAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
102 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4005094	25 mg/kg single, rectal dose: 25 mg/kg route of administration: Rectal experiment type: SINGLE co-administered:	METHOHEXITAL plasma	Homo sapiens population: HEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
27.1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17171861	1 % single, intravenous dose: 1 % route of administration: Intravenous experiment type: SINGLE co-administered:		METHOHEXITAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg/kg single, rectal Dose: 30 mg/kg Route: rectal Route: single Dose: 30 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7486084	unhealthy, 2.6 + 2.2 years Health Status: unhealthy Age Group: 2.6 + 2.2 years Sources: https://pubmed.ncbi.nlm.nih.gov/7486084	Other AEs: Airways obstruction, Transient nocturnal oxygen desaturation... Other AEs: Airways obstruction (4%) Transient nocturnal oxygen desaturation (4%) Sources: https://pubmed.ncbi.nlm.nih.gov/7486084
2 mg/mL single, intravenous Dose: 2 mg/mL Route: intravenous Route: single Dose: 2 mg/mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf	Disc. AE: Seizures, Hepatic dysfunction NOS... AEs leading to discontinuation/dose reduction: Seizures Hepatic dysfunction NOS (severe) Instability cardiovascular (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf

AEs

AE	Significance	Dose	Population
Airways obstruction	4%	30 mg/kg single, rectal Dose: 30 mg/kg Route: rectal Route: single Dose: 30 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7486084	unhealthy, 2.6 + 2.2 years Health Status: unhealthy Age Group: 2.6 + 2.2 years Sources: https://pubmed.ncbi.nlm.nih.gov/7486084
Transient nocturnal oxygen desaturation	4%	30 mg/kg single, rectal Dose: 30 mg/kg Route: rectal Route: single Dose: 30 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7486084	unhealthy, 2.6 + 2.2 years Health Status: unhealthy Age Group: 2.6 + 2.2 years Sources: https://pubmed.ncbi.nlm.nih.gov/7486084
Seizures	Disc. AE	2 mg/mL single, intravenous Dose: 2 mg/mL Route: intravenous Route: single Dose: 2 mg/mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf
Hepatic dysfunction NOS	severe Disc. AE	2 mg/mL single, intravenous Dose: 2 mg/mL Route: intravenous Route: single Dose: 2 mg/mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf
Instability cardiovascular	severe Disc. AE	2 mg/mL single, intravenous Dose: 2 mg/mL Route: intravenous Route: single Dose: 2 mg/mL Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/011559s057lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087	inducer 440		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Ca2+ channels 59 K+ channels 73	P-gp 2052	CYP450 32 CYP2C19 329

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inducer 1966 Sources: https://www.preprints.org/manuscript/202101.0503/v1 Page: 3.0	likely
CYP2C9 2497	inducer 1966 Sources: https://www.preprints.org/manuscript/202101.0503/v1 Page: 3.0	likely
CYP3A4 2633	inducer 1966 Sources: https://www.preprints.org/manuscript/202101.0503/v1 Page: 3.0	likely
CYP450 41	inducer 1966 Sources: https://www.sciencedirect.com/science/article/pii/S0964830507001357?casa_token=n3VDv5F_gzIAAAAA:KWTjWuNmeeRO91efwtuBP3yFfWC_YVihR2bHjW-fqlk9jvRcMJF1SR78eON7dhNBcXayOApQOTck Page: 276.0	yes
Ca2+ channels 62	inhibitor 4027 Sources: https://pubs.asahq.org/anesthesiology/article/88/6/1643/36862 Page: 1643.0	yes
K+ channels 73	inhibitor 4027 Sources: https://link.springer.com/article/10.1007/s12264-018-0239-1 Page: 891.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://www.sciencedirect.com/science/article/pii/S0378427412014415?casa_token=Db5SC_xlq-cAAAAA:g9nxoZoEmkyIEXEUh2LAwn-lOA0C8xtQwJ6bt8nGEkA16sxYbjsTFbmg_U01FXFVoRQuU6_CyLZX Page: 138.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubs.asahq.org/anesthesiology/article/97/1/265/40105 Page: 265.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:102216	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:102216
ChemicalBook	CB1492534	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1492534
eMolecules	3716061	https://www.emolecules.com/cgi-bin/more?vid=3716061

PubMed

Title	Date	PubMed
Transient global amnesia after ablation of premature ventricular beats arising from the right coronary cusp.	2010-08-15	20811539
Surface area of particle administered versus mass in determining the pulmonary toxicity of ultrafine and fine carbon black: comparison to ultrafine titanium dioxide.	2009-05-04	19413904
Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area.	2008-12-01	19046442
Seizures during intracarotid methohexital and amobarbital testing.	2007-02	17049312
Colorectal distension-induced pseudoaffective changes as indices of nociception in the anesthetized female rat: morphine and strain effects on visceral sensitivity.	2006-09-16	17257861
Orchiectomy or androgen receptor blockade attenuates baroreflex-mediated bradycardia in conscious rats.	2006-01-23	16430770
Effect of testosterone replacement or duration of castration on baroreflex bradycardia in conscious rats.	2005-03-30	15799780
Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins ras and rac-1.	2004-12	15263067
Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns.	2000-04	10809268
Alfentanil decreases the excitatory phenomena of sodium methohexital.	1998-09	9793810
Clonidine and methohexital-induced epileptic magnetoencephalographic discharges in patients with focal epilepsies.	1998-08	9701374
A prospective evaluation of the safety and efficacy of methohexital in the emergency department.	1996-07	8768153
A prospective study of rectal methohexital: efficacy and side effects in 648 cases.	1995-11	7486084
The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy.	1995-09	7653829
Spontaneous seizure after concurrent use of methohexital anesthesia for electroconvulsive therapy and paroxetine: a case report.	1995-02	7844577
Rectal methohexital causing apnea in two patients with meningomyeloceles.	1991-06	2042766
Pain on injection of methohexitone. The use of lignocaine to modify pain on injection of methohexitone during anaesthesia for electroconvulsive therapy.	1989-08	2782576
Drugs as allergens: the molecular basis of IgE binding to thiopentone.	1987	3654008
[Generalized seizure induced by methohexital].	1987	3109283
Seizure duration in unilateral electroconvulsive therapy. A comparison of the anaesthetic agents etomidate and Althesin with methohexitone.	1984-06	6741597
[Electroclinical aspects of intramuscular methohexital anesthesia in children].	1982-11	7156448
Severe respiratory depression following pentazocine and methohexitone. A case report.	1982-10	6961534
The prevention of pain on injection. A study of the effect of intravenous lignocaine before methohexitone.	1981-09	7030121
Seizures induced by methohexital.	1981-04	7212335
Identification of speech lateralization by intracarotid injection of methohexital.	1978-07	697329
Methohexitone-induced convulsions in epileptics.	1977-08	900462
A comparative study of etomidate and methohexital as induction agents for analgesic anesthesia.	1976	1015219
A rare allergic reaction to sodium methohexital.	1972-12	4508220
Acute allergic reaction associated with methohexital anesthesia: report of six cases.	1972-12	4508219
Intramuscular sodium methohexital as a sole pediatric anesthetic-analgesic agent.	1972-11-01	4564636
Methohexitone and thiopentone. Response to stimuli and incidence of some side effects.	1971-10	5115033
Activation of the electroencephalogram with intravenous Brietal (methohexitone): the findings in 100 cases.	1971-10	5001158
Factors in arrhythmia during dental outpatient general anesthesia.	1970-09-01	5534427
Clinical studies on induction agents. 28. A further comparison of venous complications following thiopentone, methohexitone and propanidid.	1969-08	4897470
Methohexitone and propanidid. A comparative investigation of the side effects.	1969-02	5774518
Placental transfer of tubocurarine. Case report.	1968-06	5690286

Patents

Sample Use Guides

In Vivo Use Guide

Dosage is highly individualized: the drug should be administered only by those completely familiar with its quantitative differences from other barbiturate anesthetics. Adult: brevital sodium (METHOHEXITAL SODIUM) is administered intravenously in a concentration of no higher than 1%. Higher concentrations markedly increase the incidence of muscular movements and irregularities in respiration and blood pressure. Induction of anesthesia: a 1% solution is administered at a rate of about 1 mL/5 seconds. Gaseous anesthetics and/or skeletal muscle relaxants may be administered concomitantly. The dose required for induction may range from 50 to 120 mg or more but averages about 70 mg. The usual dosage in adults ranges from 1 to 1.5 mg/kg. The induction dose usually provides anesthesia for 5 to 7 minutes. Maintenance of anesthesia: may be accomplished by intermittent injections of the 1% solution or, more easily, by continuous intravenous drip of a 0.2% solution. Intermittent injections of about 20 to 40 mg (2 to 4 mL of a 1% solution) may be given as required, usually every 4 to 7 minutes. For continuous drip, the average rate of administration is about 3 mL of a 0.2% solution/minute (1 drop/second). The rate of flow must be individualized for each patient. For longer surgical procedures, gradual reduction in the rate of administration is recommended Pediatric Patients: Brevital Sodium is administered intramuscularly in a 5% concentration and administered rectally as a 1% solution. Induction of anesthesia: by the intramuscular route of administration, the usual dose ranges from 6.6 to 10 mg/kg of the 5% concentration. For rectal administration, the usual dose for induction is 25 mg/kg using the 1% solution.

Route of Administration: Other

In Vitro Use Guide

To explore the mechanism by which methohexital (MTH) activates epileptiform activity in patients with epilepsy, it was examined the effects of MTH on hippocampal CA1 and neocortical neurons via extracellular and whole-cell patch-clamp recordings in rat brain slices. Perfusion of slices with 10 to 100 microM MTH caused no significant change in glutamatergic transmission in the hippocampal CA1 region, but enhanced gamma-aminobutyric acid (GABA)A-mediated inhibitory postsynaptic currents and induced spontaneous inhibitory postsynaptic currents in neocortical and hippocampal CA1 neurons. In addition, MTH induced a tonic, bicuculline-sensitive hyperpolarization in association with increases in membrane conductance, suggesting a direct stimulation of GABAA receptors by MTH. Spontaneous epileptiform activity was not observed in the neocortex and hippocampus after exposure of slices to MTH, neither in the standard in vitro condition nor in the presence of 4-aminopyridine, which promotes rhythmic synaptic activities.

Name

Type

Language

METHOHEXITAL SODIUM SALT

Preferred Name

English

METHOHEXITAL SODIUM

Common Name

English

Sodium 5-allyl-1-methyl-5-(1-methyl-2-pentynyl)barbiturate

Systematic Name

English

METHOHEXITAL SODIUM [USP IMPURITY]

Common Name

English

2,4,6(1H,3H,5H)-PYRIMIDINETRIONE, 1-METHYL-5-(1-METHYL-2-PENTYNYL)-5-(2-PROPENYL)-, (±)-, MONOSODIUM SALT

Common Name

English

METHOHEXITAL SODIUM [ORANGE BOOK]

Common Name

English

METHOHEXITAL SODIUM SALT [MI]

Common Name

English

BREVITAL SODIUM

Brand Name

English

METHOHEXITAL SODIUM [MART.]

Common Name

English

METHOHEXITAL SODIUM [VANDF]

Common Name

English

Methohexital sodium [WHO-DD]

Common Name

English

SODIUM METHOHEXITAL

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67084