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{{short description|Chemical compound}} |
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{{chembox |
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{{chembox |
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| verifiedrevid = 443424048 |
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| verifiedrevid = 444387711 |
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| ImageFile = Biguanide.svg |
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| ImageFile = Biguanide.svg |
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| ImageFile_Ref = {{chemboximage|correct|??}} |
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| ImageName = Skeletal formula |
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| ImageSize = 160 |
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| ImageFile1 = Biguanide-3D-balls.png |
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| ImageName = Skeletal formula of biguanide |
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| ImageName1 = Ball-and-stick model |
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| ImageFile1 = Biguanide-from-xtal-3D-bs-17.png |
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|IUPACName=imidodicarbonimidic diamide |
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| ImageFile1_Ref = {{chemboximage|correct|??}} |
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|OtherNames=Diguanide, 2-carbamimidoylguanidine |
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| ImageSize1 = 160 |
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|Section1= {{Chembox Identifiers |
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| ImageName1 = Ball and stick model of biguanide |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| PIN = Imidodicarbonimidic diamide<ref>{{cite book |author=] |date=2014 |title=Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 |publisher=] |pages=885 |doi=10.1039/9781849733069 |isbn=978-0-85404-182-4}}</ref> |
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|Section1={{Chembox Identifiers |
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| CASNo = 56-03-1 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = FB4Q52I9K2 |
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| PubChem = 5939 |
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| ChemSpiderID = 5726 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| EINECS = 200-251-8 |
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| KEGG = C07672 |
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| KEGG = C07672 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| InChIKey = XNCOSPRUTUOJCJ-UHFFFAOYAU |
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| ChEBI = 3095 |
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| SMILES1 = C(=NC(=N)N)(N)N |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| Beilstein = 507183 |
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| Gmelin = 240093 |
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| SMILES = N=C(N)NC(=N)N |
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| StdInChI = 1S/C2H7N5/c3-1(4)7-2(5)6/h(H7,3,4,5,6,7) |
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| StdInChI = 1S/C2H7N5/c3-1(4)7-2(5)6/h(H7,3,4,5,6,7) |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = XNCOSPRUTUOJCJ-UHFFFAOYSA-N |
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| StdInChIKey = XNCOSPRUTUOJCJ-UHFFFAOYSA-N |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| CASNo=56-03-1 |
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| PubChem=5939 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 3095 |
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| SMILES = C(=N)(N)NC(=N)N |
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| InChI=1/C2H7N5/c3-1(4)7-2(5)6/h(H7,3,4,5,6,7) |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID=5726 |
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}} |
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|Section2= {{Chembox Properties |
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| Formula=C<sub>2</sub>H<sub>7</sub>N<sub>5</sub> |
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| MolarMass=101.11 g/mol |
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| Appearance= |
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| Density= |
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}} |
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|Section3= {{Chembox Hazards |
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}} |
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|Section2={{Chembox Properties |
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]]] |
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| C=2 | H=7 | N=5 |
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]. Note extra ] at bottom right.]] |
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| pKa = 3.07, 13.25 |
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]. Note extra ] at right.]] |
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}} |
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'''Biguanide''' can refer to a molecule, or to a class of drugs based upon this molecule. Biguanides can function as oral antihyperglycemic ]s used for ] or ] treatment. They are also used as ]s. |
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|Section3={{Chembox Related |
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| OtherCompounds = |
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}} |
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}} |
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'''Biguanide''' ({{IPAc-en|b|aɪ|ˈ|g|w|ɒ|n|aɪ|d}}) is the organic compound with the formula HN(C(NH)NH<sub>2</sub>)<sub>2</sub>. It is a colorless solid that dissolves in water to give a highly basic solution. These solutions slowly hydrolyse to ] and ].<ref name=Ullmann>{{cite book | vauthors = Güthner T, Mertschenk B, Schulz B | chapter = Guanidine and Derivatives | title = Ullmann's Encyclopedia of Industrial Chemistry | date = 2006 | publisher = Wiley-VCH | location = Weinheim | doi = 10.1002/14356007.a12_545.pub2 | isbn = 3527306730 }}</ref> |
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==Synthesis== |
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Biguanide can be obtained from the reaction of ] with ], via a ]-type process. |
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:<math>\mathrm{C_2H_4N_4 + NH_3 \longrightarrow C_2H_7N_5}</math> |
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Biguanide was first synthesized by ] in 1879.<ref>{{cite journal |last1=Rathke |first1=B. |title=Ueber Biguanid |journal=Berichte der Deutschen Chemischen Gesellschaft |date=January 1879 |volume=12 |issue=1 |pages=776–784 |doi=10.1002/cber.187901201219|url=https://zenodo.org/record/2048781 }}</ref> |
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==Biguanidine drugs== |
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A variety of ] of biguanide are used as pharmaceutical drugs. |
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===Antihyperglycemic agents=== |
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The disinfectant ] (PAPB) features biguanide functional groups. |
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The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic ]s used for ] or ] treatment.<ref>{{cite book | vauthors = Rang HP, Dale MM, Ritter KM, Moore PK |title=Pharmacology |date=2003 |publisher=Churchill Livingstone |location=Edinburgh |isbn=0-443-07145-4 |edition=5th | page = 388}}</ref> |
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==Examples== |
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Examples include: |
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Examples of biguanides: |
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* ] - widely used in treatment of ] |
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* ] - widely used in treatment of ] |
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* ] - withdrawn from the market in most countries due to toxic effects |
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* ] - withdrawn from the market in most countries due to toxic effects |
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* ] - withdrawn from the market due to toxic effects |
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* ] - withdrawn from the market due to toxic effects |
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* ] - an ]. |
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<gallery caption="bioactive biguanidines" widths="180px" heights="120px" perrow="3"> |
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==History== |
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File:Metformin.svg|], could be referred to as asymmetric dimethylbiguanidine |
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'']'' (French lilac) was used for diabetes treatment in traditional medicine for centuries. In the 1920s, ] compounds were discovered in ''Galega'' extracts. Animal studies showed that these compounds lowered blood glucose levels. Some less toxic derivatives, ] A and synthalin B, were used for diabetes treatment, but after the discovery of ] they were forgotten for the next several decades. Biguanides were reintroduced into Type 2 ] treatment in the late 1950s. Initially ] was widely used, but its potential for sometimes fatal ] resulted in its withdrawal from pharmacotherapy in most pharmacopeias (in the U.S. in 1977). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide. |
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File:Buformin.svg|]. A ] derivative of biguanidine. |
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File:Phenformin.svg|]. A phenethylated biguanidine. |
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</gallery> |
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==Pharmacotherapy== |
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====History==== |
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{{details|metformin#History}} |
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Biguanides do not affect the output of insulin, unlike other ]s such as ]s and ]s. Therefore, not only are they effective in Type 2 diabetics but they can also be effective in Type 1 patients in concert with insulin therapy. |
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'']'' (French lilac) was used in diabetes treatment for centuries.<ref name = Witters>{{cite journal |author=Witters L |title=The blooming of the French lilac |journal=J Clin Invest |volume=108 |issue=8 |pages=1105–7 |year=2001 |pmid=11602616 |doi=10.1172/JCI14178 |pmc=209536 |url=}}</ref> In the 1920s, ] compounds were discovered in ''Galega'' extracts. Animal studies showed that these compounds lowered blood glucose levels. Some less toxic derivatives, ] A and synthalin B, were used for diabetes treatment, but after the discovery of ], their use declined. Biguanides were reintroduced into Type 2 ] treatment in the late 1950s. Initially ] was widely used, but its potential for sometimes fatal ] resulted in its withdrawal from most pharmacopeias (in the U.S. in 1978).<ref name=Tonascia1986>{{cite book | vauthors = Tonascia S, Meinert CL |title=Clinical trials: design, conduct, and analysis |publisher=Oxford University Press |location=Oxford |year=1986 |pages=53–54, 59 |isbn=0-19-503568-2}}</ref> Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide. |
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==Mechanism of action== |
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====Mechanism of action==== |
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The ] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.{{cn|date=January 2024}} |
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The ] of biguanides is not fully understood. However, in hyperinsulinemia, biguanides can lower fasting levels of insulin in plasma. Their therapeutic uses derive from their tendency to reduce ] in the liver, and, as a result, reduce the level of glucose in the blood. Biguanides also tend to make the cells of the body more willing to absorb glucose already present in the blood stream, and there again reducing the level of glucose in the plasma. |
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Biguanides do not affect the output of insulin, unlike other ]s such as ]s and ]s. Therefore, they are effective in Type 2 diabetics; and in Type 1 diabetes when used in conjunction with insulin therapy.{{cn|date=January 2024}} |
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==Side effects and toxicity== |
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The most common side effect is ] and dyspepsia, occurring in up to 30% of patients. The most important and serious side effect is ], therefore metformin is contraindicated in renal insufficiency. Renal functions should be assessed before starting metformin. Phenformin and buformin are more prone to cause acidosis than metformin; therefore they have been practically replaced by it. However, when metformin is combined with other drugs (combination therapy), ] and other side effects are possible. |
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Mainly used in Type II diabetes, metformin is considered to increase insulin sensitivity in vivo, resulting in reduced plasma glucose concentrations, increased glucose uptake, and decreased gluconeogenesis.{{cn|date=January 2024}} |
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==References== |
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{{No footnotes|date=January 2011}} |
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* Rang et al., ''Pharmacology'', 5th Edition, 2003, p 388 |
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{{Reflist}} |
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However, in hyperinsulinemia, biguanides can lower fasting levels of insulin in plasma. Their therapeutic uses derive from their tendency to reduce ] in the liver, and, as a result, reduce the level of glucose in the blood. Biguanides also tend to make the cells of the body more willing to absorb glucose already present in the bloodstream, and there again reducing the level of glucose in the plasma.{{cn|date=January 2024}} |
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{{Oral hypoglycemics}} |
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{{Antimalarials}} |
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Biguanides have been shown to interact with copper, specifically in mitochondria, where they interfere with cell metabolism by chelating Copper in its 2+ oxidation state (Cu(II)).<ref>{{cite journal |last1=Solier |first1=Stéphanie |last2=Müller |first2=Sebastian |last3=Tatiana |first3=Cañeque |last4=Antoine |first4=Versini |last5=Arnaud |first5=Mansart |last6=Fabien |first6=Sindikubwabo |last7=Leeroy |first7=Baron |last8=Laila |first8=Emam |last9=Pierre |first9=Gestraud |last10=G. Dan |first10=Pantoș |last11=Vincent |first11=Gandon |last12=Christine |first12=Gaillet |last13=Ting-Di |first13=Wu |last14=Florent |first14=Dingli |last15=Damarys |first15=Loew |last16=Sylvain |first16=Baulande |last17=Sylvère |first17=Durand |last18=Valentin |first18=Sencio |last19=Cyril |first19=Robil |last20=François |first20=Trottein |last21=David |first21=Péricat |last22=Emmanuelle |first22=Näser |last23=Céline |first23=Cougoule |last24=Etienne |first24=Meunier |last25=Anne-Laure |first25=Bègue |last26=Hélène |first26=Salmon |last27=Nicolas |first27=Manel |last28=Alain |first28=Puisieux |last29=Sarah |first29=Watson |last30=Mark A. |first30=Dawson |last31=Nicolas |first31=Servant |last32=Guido |first32=Kroemer |last33=Djillali |first33=Annane |last34=Raphaël |first34=Rodriguez |title=A druggable copper-signalling pathway that drives inflammation |journal=Nature |date=2023 |pages=1-9 |doi=10.1038/s41586-023-06017-4 |pmid=37100912 |url=https://www.nature.com/articles/s41586-023-06017-4|pmc=10131557 }}</ref> |
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====Side effects and toxicity==== |
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] |
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The most common side effect is ] and dyspepsia, occurring in up to 30% of patients. The most important and serious side effect is ], therefore metformin is contraindicated in advanced ]. Kidney function should be assessed before starting metformin. Phenformin and buformin are more prone to cause acidosis than metformin; therefore they have been practically replaced by it. However, when metformin is combined with other drugs (combination therapy), ] and other side effects are possible.{{cn|date=January 2024}} |
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===Antimalarial=== |
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] |
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During WWII a British team led by ] discovered (see details there) that some biguanides are useful as ]s. Much later it was demonstrated that they are prodrugs metabolised into active ] derivatives which, until recently, were believed to work by ] ]. Examples include:{{cn|date=January 2024}} |
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* ] (>]) |
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* ] |
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===Disinfectants=== |
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{{see also|Bisbiguanide}} |
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The disinfectants ], ] (PAPB), ], and ] feature biguanide ]s.<ref>{{cite journal | vauthors = Tanzer JM, Slee AM, Kamay BA | title = Structural requirements of guanide, biguanide, and bisbiguanide agents for antiplaque activity | journal = Antimicrobial Agents and Chemotherapy | volume = 12 | issue = 6 | pages = 721–9 | date = December 1977 | pmid = 931371 | pmc = 430011 | doi = 10.1128/aac.12.6.721 }}</ref> |
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== References == |
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{{reflist}} |
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{{oral hypoglycemics}} |
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{{antimalarials}} |
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] |
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] |