View source for Methohexital

{{Short description|Anesthetic and barbiturate-type sedative}}
{{Use American English|date=July 2024}}
{{Drugbox
| verifiedrevid = 462249932
| image = Methohexital.svg
| alt = Skeletal formula
| image2 = Methohexital-from-xtal-3D-bs-17.png
| alt2 = Ball-and-stick model

<!--Clinical data-->
| synonyms  = Methohexitone
| tradename = Brevital Sodium
| class     = [[Barbiturate]]
| Drugs.com = {{drugs.com|CDI|methohexital}}
| DailyMedID = Methohexital
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_US      = C
| pregnancy_US_comment = 
| pregnancy_category = 
| legal_AU = S4
| legal_US = Schedule IV
| legal_US_comment = <ref name="Brevital Sodium FDA label" />
| legal_status = 
| routes_of_administration = [[Intravenous]], [[Rectal administration|rectal]]
| ATC_prefix = N01
| ATC_suffix = AF01
| ATC_supplemental = {{ATC|N05|CA15}}

<!--Pharmacokinetic data-->
| bioavailability = I.V. ~100%<br>Rectal ~17%
| metabolism = [[Liver]]
| elimination_half-life = 5.6 ± 2.7 minutes
| excretion = excreted in feces

<!--Identifiers-->
| IUPHAR_ligand = 7233
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 151-83-7
| PubChem = 9034
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00474
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 8683
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = E5B8ND5IPE
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D04985
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 102216
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 7413

<!--Chemical data-->
| IUPAC_name = 5-Hex-3-yn-2-yl-1-methyl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione
| C=14 | H=18 | N=2 | O=3
| smiles = O=C1N(C(=O)NC(=O)C1(C\C=C)C(C#CCC)C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NZXKDOXHBHYTKP-UHFFFAOYSA-N
}}

'''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.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/mesh/68008723|title=Methohexital|website=MeSH}}</ref> It is similar in its effects to [[sodium thiopental]], a drug with which it competed in the market for [[anesthetics]].

==Pharmacology==
Methohexital binds to a distinct site which is associated with Cl<sup>−</sup> [[ionophore]]s at GABA<sub>A</sub> receptors.<ref>{{cite book | vauthors = Katzung BG | title = Basic and Clinical Pharmacology | edition = 10th | pages = 406–407}}</ref> This increases the length of time which the Cl<sup>−</sup> ionopores are open, thus causing an [[Inhibitory postsynaptic potential|inhibitory]] effect.

Metabolism of methohexital is primarily hepatic via demethylation and oxidation.<ref name="Brevital Sodium FDA label">{{Cite web|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eccd8340-ead3-4363-8902-0c19d33aa2ac|title=Brevital Sodium |date= July 24, 2019|website=DailyMed|access-date= November 20, 2019}}</ref> 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.<ref name="Brevital Sodium FDA label" />  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).<ref name=Schulgasser>{{cite journal | vauthors = Schulgasser H, Borowitz AH | title = Methohexital anaesthesia in electroconvulsive therapy | journal = South African Medical Journal | volume = 37 | pages = 870–1 | date = August 1963 | pmid = 14045806 }}</ref> 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.<ref name=Schulgasser/>

==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]].<ref>{{cite patent | title = 1,5,5-Trisubstituted barbituric acids | inventor = Doran WJ | assign1 = Eli Lily and Company | country = US | number = 2872448 | gdate = February 3, 1959 }} ({{US Patent|2872448}})</ref> 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.

:[[File:Methohexital synthesis.png|800px|left|thumb|Methohexital synthesis]]{{clear-left}}

== References ==
{{Reflist}}

== External links ==
{{Commons category}}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/151-83-7 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Methohexital }}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/methohexital%20sodium | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Methohexital sodium }}

{{Anesthesia}}
{{General anesthetics}}
{{Hypnotics and sedatives}}
{{GABAAR PAMs}}
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[[Category:Barbiturates]]
[[Category:General anesthetics]]
[[Category:Allyl compounds]]
[[Category:Alkyne derivatives]]