 | |
 | |
| Names | |
|---|---|
| Preferred IUPAC name Imidodicarbonimidic diamide[1] | |
| Identifiers | |
| |
3D model (JSmol) | |
| 507183 | |
| ChEBI | |
| ChemSpider |
|
| ECHA InfoCard | 100.000.229 |
| EC Number |
|
| 240093 | |
| KEGG |
|
| UNII | |
| |
| |
| Properties | |
| C2H7N5 | |
| Molar mass | 101.113 g·mol−1 |
| Acidity (pKa) | 3.07, 13.25 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Biguanide (/baɪˈɡwɒnaɪd/) is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give a highly basic solution. These solutions slowly hydrolyse toammonia andurea.[2]
Biguanide can be obtained from the reaction ofdicyandiamide withammonia, via aPinner-type process.
Biguanide was first synthesized byBernhard Rathke in 1879.[3]
A variety ofderivatives of biguanide are used as pharmaceutical drugs.
The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemicdrugs used fordiabetes mellitus orprediabetes treatment.[4]
Examples include:
Galega officinalis (French lilac) was used in diabetes treatment for centuries.[5] In the 1920s,guanidine compounds were discovered inGalega extracts. Animal studies showed that these compounds lowered blood glucose levels. Some less toxic derivatives,synthalin A and synthalin B, were used for diabetes treatment, but after the discovery ofinsulin, their use declined. Biguanides were reintroduced into Type 2diabetes treatment in the late 1950s. Initiallyphenformin was widely used, but its potential for sometimes fatallactic acidosis resulted in its withdrawal from most pharmacopeias (in the U.S. in 1978).[6] Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.
Themechanism of action of biguanides is not fully understood, and many mechanisms have been proposed for metformin.[citation needed]
Biguanides do not affect the output of insulin, unlike otherhypoglycemic agents such assulfonylureas andmeglitinides. Therefore, they are effective in Type 2 diabetics; and in Type 1 diabetes when used in conjunction with insulin therapy.[citation needed]
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.[citation needed]
However, in hyperinsulinemia, biguanides can lower fasting levels of insulin in plasma. Their therapeutic uses derive from their tendency to reducegluconeogenesis 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.[citation needed]
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)).[7]
The most common side effect isdiarrhea and dyspepsia, occurring in up to 30% of patients. The most important and serious side effect islactic acidosis, therefore metformin is contraindicated in advancedchronic kidney disease. 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),hypoglycemia and other side effects are possible.[citation needed]
During WWII a British team led byFrank Rose discovered (see details there) that some biguanides are useful asantimalarial drugs. Much later it was demonstrated that they are prodrugs metabolised into activedihydrotriazine derivatives which, until recently, were believed to work byinhibitingdihydrofolate reductase. Examples include:[citation needed]
The disinfectantschlorhexidine,polyaminopropyl biguanide (PAPB),polihexanide, andalexidine feature biguanidefunctional groups.[8]
