Methohexital

Last updated
Methohexital
Methohexital.svg
Methohexital-SbRh-from-xtal-2003.png
Clinical data
Trade names Brevital Sodium
Other namesMethohexitone
AHFS/Drugs.com Consumer Drug Information
License data
Routes of
administration
Intravenous, rectal
Drug class Barbiturate
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability I.V. ~100%
Rectal ~17%
Metabolism Liver
Elimination half-life 5.6 ± 2.7 minutes
Excretion excreted in feces
Identifiers
  • 5-Hex-3-yn-2-yl-1-methyl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.005.272 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C14H18N2O3
Molar mass 262.309 g·mol−1
3D model (JSmol)
  • O=C1N(C(=O)NC(=O)C1(C\C=C)C(C#CCC)C)C
  • InChI=1S/C14H18N2O3/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) Yes check.svgY
  • Key:NZXKDOXHBHYTKP-UHFFFAOYSA-N Yes check.svgY
   (verify)

Methohexital or methohexitone (marketed under the brand names Brevital and Brietal) is a drug which is a barbiturate derivative. It is classified as short-acting, and has a rapid onset of action. [2] It is similar in its effects to sodium thiopental, a drug with which it competed in the market for anaesthetics.

Contents

Pharmacology

Methohexital binds to a distinct site which is associated with Cl ionophores at GABAA receptors. [3] This increases the length of time which the Cl ionopores are open, thus causing an inhibitory effect.

Metabolism of methohexital is primarily hepatic via demethylation and oxidation. [1] Side-chain oxidation is the primary means of metabolism involved in the termination of the drug's biological activity.

Indications

Methohexital is primarily used to induce anesthesia, and is generally provided as a sodium salt (i.e. methohexital sodium). It is only used in hospital or similar settings, under strict supervision. [1] It has been commonly used to induce deep sedation or general anesthesia for surgery and dental procedures. Unlike many other barbiturates, methohexital actually lowers the seizure threshold, a property that makes it particularly useful when anesthesia is provided for an electroconvulsive therapy (ECT). [4] Its rapid recovery rate with consciousness being gained within three to seven minutes after induction and full recovery within 30 minutes is a major advantage over other ECT barbiturates. [4]

Synthesis

Methohexital can be synthesized in the classic manner of making barbituric acid derivatives, in particular by the reaction of malonic ester derivatives with derivatives of urea. [5] The resulting allyl-(1-methyl-2-pentynyl) malonic ester is synthesized by subsequent alkylation of the malonic ester itself, beginning with 2-bromo-3-hexyne, which gives (1-methyl-2-pentynyl)malonic ester, and then by allylbromide. In the final step, reaction of the disubstituted malonic ester with N-methylurea gives methohexital.

Methohexital synthesis Methohexital synthesis.png
Methohexital synthesis

Related Research Articles

Pyrimidine is an aromatic, heterocyclic, organic compound similar to pyridine. One of the three diazines, it has nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine and pyridazine.

<span class="mw-page-title-main">Sodium thiopental</span> Barbiturate general anesthetic

Sodium thiopental, also known as Sodium Pentothal, thiopental, thiopentone, or Trapanal, is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of pentobarbital, and an analog of thiobarbital. Sodium thiopental was a core medicine in the World Health Organization's List of Essential Medicines, but was supplanted by propofol. Despite this, thiopental is listed as an acceptable alternative to propofol, depending on local availability and cost of these agents. It was previously the first of three drugs administered during most lethal injections in the United States, but the US manufacturer Hospira stopped manufacturing the drug in 2011 and the European Union banned the export of the drug for this purpose. Although thiopental abuse carries a dependency risk, its recreational use is rare.

<span class="mw-page-title-main">Procaine</span> Local anesthetic drug

Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity of the trade name Novocain or Novocaine, in some regions, procaine is referred to generically as novocaine. It acts mainly as a sodium channel blocker. Today, it is used therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion-enhancing, and mood-enhancing effects.

<span class="mw-page-title-main">Malonic acid</span> Carboxylic acid with chemical formula CH2(COOH)2

Malonic acid (IUPAC systematic name: propanedioic acid) is a dicarboxylic acid with structure CH2(COOH)2. The ionized form of malonic acid, as well as its esters and salts, are known as malonates. For example, diethyl malonate is malonic acid's diethyl ester. The name originates from the Greek word μᾶλον (malon) meaning 'apple'.

<span class="mw-page-title-main">Diethyl malonate</span> Chemical compound

Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds such as barbiturates, artificial flavourings, vitamin B1, and vitamin B6.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<span class="mw-page-title-main">Amobarbital</span> Barbiturate

Amobarbital is a drug that is a barbiturate derivative. It has sedative-hypnotic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923. It is considered a short to intermediate acting barbiturate. If amobarbital is taken for extended periods of time, physiological and psychological dependence can develop. Amobarbital withdrawal mimics delirium tremens and may be life-threatening. Amobarbital was manufactured by Eli Lilly and Company in the US under the brand name Amytal in bright blue bullet shaped capsules or pink tablets containing 50, 100, or 200 milligrams of the drug. The drug was also manufactured generically. Amobarbital was widely misused, known as "Blue Heavens" on the street. Amytal, as well as Tuinal, a combination drug containing equal quantities of secobarbital and amobarbital, were both manufactured by Eli Lilly until the late-1990s. However, as the popularity of benzodiazepines increased, prescriptions for these medications became increasingly rare beginning in the mid to late-1980s.

<span class="mw-page-title-main">Phenobarbital</span> Medication of the barbiturate type

Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of epilepsy in developing countries. In the developed world, it is commonly used to treat seizures in young children, while other medications are generally used in older children and adults. In developed countries it is used for veterinary purposes. It may be used intravenously, injected into a muscle, or taken by mouth. The injectable form may be used to treat status epilepticus. Phenobarbital is occasionally used to treat trouble sleeping, anxiety, and drug withdrawal and to help with surgery. It usually begins working within five minutes when used intravenously and half an hour when administered by mouth. Its effects last for between four hours and two days.

In organic chemistry, the Michael reaction or Michael addition is a reaction between a Michael donor and a Michael acceptor to produce a Michael adduct by creating a carbon-carbon bond at the acceptor's β-carbon. It belongs to the larger class of conjugate additions and is widely used for the mild formation of carbon-carbon bonds.

Barbituric acid or malonylurea or 6-hydroxyuracil is an organic compound based on a pyrimidine heterocyclic skeleton. It is an odorless powder soluble in water. Barbituric acid is the parent compound of barbiturate drugs, although barbituric acid itself is not pharmacologically active. The compound was first synthesised by Adolf von Baeyer.

Pentobarbital is a short-acting barbiturate typically used as a sedative, a preanesthetic, and to control convulsions in emergencies. It can also be used for short-term treatment of insomnia but has been largely replaced by the benzodiazepine family of drugs.

<span class="mw-page-title-main">Butabarbital</span> Chemical compound

Butabarbital is a prescription barbiturate sleep aid and anxiety medication. Butabarbital has a particularly fast onset of effects and short duration of action compared to other barbiturates, which makes it useful for certain applications such as treating severe insomnia, relieving general anxiety and relieving anxiety before surgical procedures; however it is also relatively dangerous particularly when combined with alcohol, and so is now rarely used, although it is still prescribed in some Eastern European and South American countries. Its intermediate duration of action gives butabarbital an abuse potential slightly lower than secobarbital. Butabarbital can be hydrolyzed to Valnoctamide.

<span class="mw-page-title-main">Benzyl benzoate</span>

Benzyl benzoate is an organic compound which is used as a medication and insect repellent. As a medication it is used to treat scabies and lice. For scabies either permethrin or malathion is typically preferred. It is applied to the skin as a lotion. Typically two to three applications are needed. It is also present in Balsam of Peru, Tolu balsam, and in a number of flowers.

The malonic ester synthesis is a chemical reaction where diethyl malonate or another ester of malonic acid is alkylated at the carbon alpha to both carbonyl groups, and then converted to a substituted acetic acid. The major drawback of malonic ester synthesis is that the alkylation stage can also produce dialkylated structures. This makes separation of products difficult and yields lower.

<span class="mw-page-title-main">Hexobarbital</span> Chemical compound

Hexobarbital or hexobarbitone, sold both in acid and sodium salt forms as Citopan, Evipan, and Tobinal, is a barbiturate derivative having hypnotic and sedative effects. It was used in the 1940s and 1950s as an agent for inducing anesthesia for surgery, as well as a rapid-acting, short-lasting hypnotic for general use, and has a relatively fast onset of effects and short duration of action. It was also used to murder women prisoners at Ravensbrück concentration camp. Modern barbiturates have largely supplanted the use of hexobarbital as an anesthetic, as they allow for better control of the depth of anesthesia. Hexobarbital is still used in some scientific research.

<span class="mw-page-title-main">Dimethyl malonate</span> Chemical compound

Dimethyl malonate is a diester derivative of malonic acid. It is a common reagent for organic synthesis used, for example, as a precursor for barbituric acid. It is also used in the malonic ester synthesis. It can be synthesized from dimethoxymethane and carbon monoxide.

Barbiturase is a zinc-containing amidohydrolase. Its systemic name is barbiturate amidohydrolase (3-oxo-3-ureidopropanoate-forming). Barbiturase acts as a catalyst in the second step of oxidative pyrimidine degradation, promoting the ring-opening hydrolysis of barbituric acid to ureidomalonic acid. Although grouped into the naturally existing amidohydrolases, it demonstrates more homology with cyanuric acid amidohydrolase. Therefore, it has been proposed that barbiturase, along with cyanuric acid, should be grouped into a new family. KEGG

<span class="mw-page-title-main">Barbiturate</span> Class of depressant drugs derived from barbituric acid

Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as well as overdose potential among other possible adverse effects. They have been used recreationally for their anti-anxiety and sedative effects, and are thus controlled in most countries due to the risks associated with such use.

Uracil/thymine dehydrogenase (EC 1.17.99.4, uracil oxidase, uracil-thymine oxidase, uracil dehydrogenase) is an enzyme with systematic name uracil:acceptor oxidoreductase. This enzyme catalyses the following chemical reaction

GABA<sub>A</sub> receptor positive allosteric modulator

In pharmacology, GABAA receptor positive allosteric modulators, also known as GABAkines or GABAA receptor potentiators, are positive allosteric modulator (PAM) molecules that increase the activity of the GABAA receptor protein in the vertebrate central nervous system.

References

  1. 1 2 3 "Brevital Sodium". DailyMed. 2019-07-24. Retrieved 2019-11-20.
  2. "Methohexital". MeSH.
  3. Katzung BG. Basic and Clinical Pharmacology (10th ed.). pp. 406–407.
  4. 1 2 Schulgasser H, Borowitz AH (August 1963). "Methohexital anaesthesia in electroconvulsive therapy". South African Medical Journal. 37: 870–1. PMID   14045806.
  5. US 2872448,Doran WJ,"1,5,5-Trisubstituted barbituric acids",issued 3 February 1959, assigned to Eli Lily and Company