Biguanide

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Biguanide
Skeletal formula of biguanide
Ball and stick model of biguanide
Names
Preferred IUPAC name
Imidodicarbonimidic diamide[1]
Identifiers
3D model (
JSmol
)
507183
ChEBI
ChemSpider
ECHA InfoCard
 100.000.229 Edit this at Wikidata
EC Number
  • 200-251-8
240093
KEGG
UNII
  • InChI=1S/C2H7N5/c3-1(4)7-2(5)6/h(H7,3,4,5,6,7) checkY
    Key: XNCOSPRUTUOJCJ-UHFFFAOYSA-N checkY
  • N=C(N)NC(=N)N
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 their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

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 highly basic solution. These solutions slowly hydrolyse to ammonia and urea.[2]

Synthesis

Biguanide can be obtained from the reaction of

dicyandiamide with ammonia, via a Pinner
-type process.

Biguanide was first synthesized by Bernhard Rathke in 1879.[3]

Biguanidine drugs

A variety of derivatives of biguanide are used as pharmaceutical drugs.

Antihyperglycemic agents

The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic

diabetes mellitus or prediabetes treatment.[4]

Examples include:

  • bioactive biguanidines
  • Metformin, could be referred to as asymmetric dimethylbiguanidine
    Metformin, could be referred to as asymmetric dimethylbiguanidine
  • Buformin. A butyl derivative of biguanidine.
    butyl
    derivative of biguanidine.
  • Phenformin. A phenethylated biguanidine.
    Phenformin. A phenethylated biguanidine.

History

Further information: metformin § History

Galega officinalis (French lilac) was used in diabetes treatment for centuries.[5] In the 1920s, guanidine compounds were discovered in Galega 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 of insulin, their use declined. Biguanides were reintroduced into Type 2 diabetes treatment in the late 1950s. Initially phenformin was widely used, but its potential for sometimes fatal lactic 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.

Mechanism of action

The mechanism 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 other

hypoglycemic agents such as sulfonylureas and meglitinides. 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 reduce gluconeogenesis 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]

Side effects and toxicity

The most common side effect is diarrhea and dyspepsia, occurring in up to 30% of patients. The most important and serious side effect is lactic acidosis, therefore metformin is contraindicated in advanced chronic 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]

Antimalarial

During WWII a British team led by

antimalarial drugs. Much later it was demonstrated that they are prodrugs metabolised into active dihydrotriazine derivatives which, until recently, were believed to work by inhibiting dihydrofolate reductase. Examples include:[citation needed
]

Disinfectants

See also: Bisbiguanide

The disinfectants

polihexanide, and alexidine feature biguanide functional groups.[8]

References

  1. ISBN 978-0-85404-182-4
    .
  2. ISBN 3527306730
    .
  3. doi:10.1002/cber.187901201219
    .
  4. ISBN 0-443-07145-4
    .
  5. PMID 11602616
    .
  6. ISBN 0-19-503568-2
    .
  7. PMID 37100912
    .
  8. PMID 931371
    .
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