Bumetanide

{{Short description|Medication for swelling and high blood pressure}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | verifiedrevid = 459985487 | image = Bumetanide structure.svg | image_class = skin-invert-image | width = 200px | image2 = Bumetanide_ball-and-stick.png | image_class2 = bg-transparent | width2 = 200px

| tradename = Bumex, Burinex, Enbumyst others | Drugs.com = {{drugs.com|monograph|bumetanide}} | MedlinePlus = a684051 | DailyMedID = Bumetanide | pregnancy_AU = B3 | routes_of_administration = By mouth, intravenous, intramuscular, intranasal | ATC_prefix = C03 | ATC_suffix = CA02 | ATC_supplemental =

| legal_AU = S4 | legal_UK = POM | legal_US = Rx-only

| IUPHAR_ligand = 4837 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 28395-03-1 | PubChem = 2471 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00887 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 2377 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 0Y2S3XUQ5H | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00247 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 3213 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1072

| IUPAC_name = 3-butylamino-4-phenoxy-5-sulfamoyl-benzoic acid | C=17 | H=20 | N=2 | O=5 | S=1 | smiles = c1ccccc1Oc2c(NCCCC)cc(C(=O)O)cc2S(=O)(=O)N | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = MAEIEVLCKWDQJH-UHFFFAOYSA-N }}

'''Bumetanide''', sold under the brand name '''Bumex''' among others, is a medication used to treat swelling and high blood pressure.<ref name=AHFS2019/> This includes swelling as a result of heart failure, liver failure, or kidney problems.<ref name=AHFS2019/> It may work for swelling when other medications have not.<ref name=AHFS2019/> For high blood pressure it is not a preferred treatment.<ref name=AHFS2019/> It is taken by mouth, or by injection into a vein or muscle.<ref name=AHFS2019>{{cite web |title=Bumetanide Monograph for Professionals |url=https://www.drugs.com/monograph/bumetanide.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=8 April 2019 |language=en}}</ref> Effects generally begin within an hour and last for about six hours.<ref name=AHFS2019/>

Common side effects include dizziness, low blood pressure, low blood potassium, muscle cramps, and kidney problems.<ref name=AHFS2019/> Other serious side effects may include hearing loss and low blood platelets.<ref name=AHFS2019/> Blood tests are recommended regularly for those on treatment.<ref name=AHFS2019/> Safety during pregnancy and breastfeeding is unclear.<ref name=Preg2019>{{cite web |title=Bumetanide (Bumex) Use During Pregnancy |url=https://www.drugs.com/pregnancy/bumetanide.html |website=Drugs.com |access-date=8 April 2019 |language=en}}</ref> Bumetanide is a loop diuretic and works by decreasing the reabsorption of sodium by the kidneys.<ref name=BNF76>{{cite book|title=British national formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=978-0-85711-338-2|pages=225–226|edition=76}}</ref><ref name=AHFS2019/>

Bumetanide was patented in 1968 and came into medical use in 1972.<ref>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=458 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA458 |language=en}}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO22nd">{{cite book | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> It is available as a generic medication.<ref name=BNF76/> In 2023, it was the 243rd most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Bumetanide - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Bumetanide | access-date = 20 August 2025}}</ref>

==Medical uses== It is used to treat swelling and high blood pressure.<ref name=AHFS2019/> This includes swelling as a result of heart failure, liver failure, or kidney problems.<ref name=AHFS2019/> For high blood pressure it is not a preferred treatment.<ref name=AHFS2019/> It is taken by mouth, or by injection into a vein or muscle.<ref name=AHFS2019/>

==Side effects== Common side effects include dizziness, low blood pressure, low blood potassium, muscle cramps, and kidney problems.<ref name=AHFS2019/> Other serious side effects may include hearing loss and low blood platelets.<ref name=AHFS2019/> A large observational study <ref>{{cite journal | vauthors = Strom BL, Schinnar R, Apter AJ, Margolis DJ, Lautenbach E, Hennessy S, Bilker WB, Pettitt D | title = Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics | journal = The New England Journal of Medicine | volume = 349 | issue = 17 | pages = 1628–1635 | date = October 2003 | pmid = 14573734 | doi = 10.1056/NEJMoa022963 | doi-access = free }}</ref> concluded that people with a sulfonamide antibiotic allergy may be allergic to sulfonamide non-antibiotics, such as bumetanide, but this is likely due to certain people being at an increased risk in general to developing allergic reactions rather than cross-reactivity between sulfonamide-containing drugs. In smaller studies, the lack of cross-reactivity between sulfonamide antibiotics and sulfonamide non-antibiotics has been demonstrated.<ref>{{cite journal | vauthors = Hemstreet BA, Page RL | title = Sulfonamide allergies and outcomes related to use of potentially cross-reactive drugs in hospitalized patients | journal = Pharmacotherapy | volume = 26 | issue = 4 | pages = 551–557 | date = April 2006 | pmid = 16553515 | doi = 10.1592/phco.26.4.551 | s2cid = 21612858 }}</ref><ref>{{cite journal | vauthors = Tornero P, De Barrio M, Baeza ML, Herrero T | title = Cross-reactivity among p-amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testing | journal = Contact Dermatitis | volume = 51 | issue = 2 | pages = 57–62 | date = August 2004 | pmid = 15373844 | doi = 10.1111/j.0105-1873.2004.00274.x | s2cid = 10908796 }}</ref>

Safety during pregnancy and breastfeeding is unclear.<ref name=Preg2019/>

== Pharmacology == === Pharmacodynamics === Bumetanide is a loop diuretic and works by decreasing the reabsorption of sodium by the kidneys. The main difference between bumetanide and furosemide is in their bioavailability and potency. About 60% of furosemide is absorbed in the intestine, and there are substantial inter- and intraindividual differences in bioavailability (range 10-90%). About 80% of bumetanide is absorbed, and its absorption does not change when it is taken with food. It is said to be a more predictable diuretic, meaning that the predictable absorption is reflected in a more predictable effect.<ref name="Brunton, Laurence 2006">{{cite book | veditors = Brunton L, Lazo JS, Parker KL |year=2006 |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics |location=New York |publisher=McGraw-Hill |isbn=0-07-142280-3 |edition=11th |pages=749–753 }}</ref> Bumetanide is 40 times more potent than furosemide for people with normal renal function.<ref name="Brunton, Laurence 2006" />

==Synthesis== Bumetanide is synthesized from 4-chlorobenzoic acid.<ref name="Ger. Pat. 19 64 503.5">{{cite patent | country = DE | number = 1964504 | title = Arzneimittelzubereitung mit einem Gehalt an 3-Butylamino-4-phenoxy-5-sulfamyl-benzoesaeure und deren Salzen | inventor = Feit PW | assign1 = Leo Pharma Products, Ltd. | gdate = 9 July 1970 }}</ref><ref name="Feit">{{cite journal | vauthors = Feit PW | title = Aminobenzoic acid diuretics. 2. 4-Substituted-3-amino-5-sulfamylbenzoic acid derivatives | journal = Journal of Medicinal Chemistry | volume = 14 | issue = 5 | pages = 432–9 | date = May 1971 | pmid = 5117690 | doi = 10.1021/jm00287a014 }}</ref><ref>{{cite patent | country = US | number = 3634583 |title=Pharmaceutical composition for the treatment of oedematous conditions and hypertension | inventor = Feit PW | assign1 = Leo Pharmaceutical Products Ltd AS | gdate = 11 January 1972 }}</ref><ref>{{cite patent | country = US | number = 4082851 | title = Sulphonamides, compositions containing the same and methods for using the same in the treatment of hypertension or odemeas | inventor = Feit PW, Nielsen OB, Bruun H, Bretting CA | assign1 = Leo Pharmaceutical Products Ltd AS | gdate = 4 April 1978 }}</ref> In the first stage of synthesis, it undergoes sulfonylchlorination by chlorosulfonic acid, forming 4-chloro-3-chlorosulfonylbenzoic acid, which is further nitrated with nitric acid to 4-chloro-3-chlorosulfonyl-5-nitrobenzoic acid. Reacting this with ammonia gives 5-aminosulfonyl-4-chloro-3-nitrobenzoic acid, which when reacted with sodium phenolate is transformed into 5-amino-sulfonyl-3-nitro-5-phenoxybenzoic acid. Reduction of the nitro group in this product by hydrogen using a palladium on carbon catalyst gives 3-amino-5-aminosulfonyl-5-phenoxybenzoic acid. Finally, reacting this with butyl alcohol in the presence of sulfuric acid, followed by treatment with sodium hydroxide to hydrolyze the butyl ester, gives the desired bumetanide.

:600px|thumb|left|Synthesis of bumetanide {{Clear}}

== Society and culture == It 2008, four National Football League players were suspended under the steroid policy as a result of taking bumetanide.<ref>{{cite web|title=McAllister, Smith, Grant, Texans' Pittman among players testing positive|url=http://www.espn.com/nfl/news/story?id=3661845|website=ESPN.com|publisher=ESPN|access-date=June 6, 2017|date=October 26, 2008}}</ref>

Bumetanide was an undisclosed active ingredient in the over-the-counter weight loss supplement StarCaps, which was removed from the market after its presence was discovered by the United States Food and Drug Administration.<ref>{{cite web| author = Food and Drug Administration Office of Criminal Investigations | work = U.S. Department of Justice Press Release | title = Pills Sold Throughout the United States Contained an Undisclosed Prescription Drug Banned By the National Football League|url=https://www.fda.gov/iceci/criminalinvestigations/ucm391757.htm |archive-url=https://web.archive.org/web/20140709002226/http://www.fda.gov/ICECI/CriminalInvestigations/ucm391757.htm |archive-date=July 9, 2014 |publisher=United States Food and Drug Administration|access-date=June 6, 2017|date=March 26, 2014}}</ref>

==Research== In the brain, bumetanide blocks the NKCC1 cation-chloride co-transporter, and thus decreases internal chloride concentration in neurons. In turn, this concentration change makes the action of GABA more hyperpolarizing, which may be useful for treatment of neonatal seizures, which quite often are not responsive to traditional GABA-targeted treatment, such as barbiturates. Bumetanide is therefore under evaluation as a prospective antiepileptic drug.<ref>{{cite journal | vauthors = Löscher W, Puskarjov M, Kaila K | title = Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments | journal = Neuropharmacology | volume = 69 | pages = 62–74 | date = June 2013 | pmid = 22705273 | doi = 10.1016/j.neuropharm.2012.05.045 | s2cid = 22267675 }}</ref>

The drug has also been studied as a treatment for autism.<ref>{{cite journal | vauthors = Sprengers JJ, van Andel DM, Zuithoff NP, Keijzer-Veen MG, Schulp AJ, Scheepers FE, Lilien MR, Oranje B, Bruining H | title = Bumetanide for Core Symptoms of Autism Spectrum Disorder (BAMBI): A Single Center, Double-Blinded, Participant-Randomized, Placebo-Controlled, Phase-2 Superiority Trial | journal = Journal of the American Academy of Child and Adolescent Psychiatry | date = July 2020 | volume = 60 | issue = 7 | pages = 865–876 | pmid = 32730977 | doi = 10.1016/j.jaac.2020.07.888 | quote = Recent trials have indicated positive effects of bumetanide in autism spectrum disorder (ASD). | doi-access = free }}</ref><ref>{{cite journal | vauthors = Zhang L, Huang CC, Dai Y, Luo Q, Ji Y, Wang K, Deng S, Yu J, Xu M, Du X, Tang Y, Shen C, Feng J, Sahakian BJ, Lin CP, Li F | title = Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios | journal = Translational Psychiatry | volume = 10 | issue = 1 | article-number = 9 | date = January 2020 | pmid = 32066666 | pmc = 7026137 | doi = 10.1038/s41398-020-0692-2 | doi-access = free }}</ref>

== References == {{reflist}}

== External links == * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/bumetanide | archive-url = https://web.archive.org/web/20170123214356/https://druginfo.nlm.nih.gov/drugportal/name/Bumetanide | archive-date = January 23, 2017 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Bumetanide }} * {{cite web | url = https://www.helsinki.fi/en/hilife-helsinki-institute-life-science/news/repurposed-drug-boosts-positive-effect-microglia-improve-cognitive-performance-following-brain-trauma | title = Repurposed drug boosts the positive effect of microglia to improve cognitive performance following brain trauma | date = 24 May 2023 }}

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