Biguanide: Difference between revisions

{{short description|Chemical compound}}

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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)NH₂)₂.  It is a colorless solid that dissolves in water to give highly basic solution.  These solutions slowly hydrolyse to [[ammonia]] and [[urea]].

Biguanide can be obtained from the reaction of [[dicyandiamide]] with [[ammonia]], via a [[pinner reaction|Pinner]]-type process.

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

A variety of [[derivative (chemistry)|derivatives]] of biguanide are used as pharmaceutical drugs.

The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic [[drug]]s used for [[diabetes mellitus]] or [[prediabetes]] treatment.

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{{details|metformin#History}}

''[[Galega officinalis]]'' (French lilac) was used in diabetes treatment for centuries. 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). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.

The [[mechanism of action]] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.

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)).

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.

During WWII a British team led by [[Frank Rose (chemist)|Frank Rose]] discovered (see details there) that some biguanides are useful as [[antimalarial drug]]s. Much later it was demonstrated that they are prodrugs metabolised into active [[dihydrotriazine]] derivatives which, until recently, were believed to work by [[Dihydrofolate reductase inhibitor|inhibiting]] [[dihydrofolate reductase]]. Examples include:

* [[Proguanil]] (>[[cycloguanil]])

* [[Chlorproguanil]]

{{see also|Bisbiguanide}}

The disinfectants [[chlorhexidine]], [[polyaminopropyl biguanide]] (PAPB), [[polihexanide]], and [[alexidine]] feature biguanide [[functional group]]s.