Biguanides

Biguanides Chemische Eigenschaften,Einsatz,Produktion Methoden

• Allgemeine Beschreibung

  The biguanide class of insulin-sensitizing agents includesonly one marketed medicinal in the United States, namelymetformin , but this drug is a first-line drug in the treatment of type 2 diabetes, for which it is prescribed heavily,alone and in combinations. Having been brought to marketin France in 1979 (though not until 1995 in the UnitedStates), metformin has a long history of use, despite whichfact the mechanisms underlying its effects remain uncertain.52–56 Activation by metformin of adenosine monophosphate-activated protein kinase (AMPK) has commonly beenstated as the molecular mechanism in recent years; however,the as-yet-to-be-identified primary target(s) must either beupstream of AMPK, or trigger downstream mechanisms thatdeliver stimulatory feedback upstream of AMPK, or causechanges in crosstalk mechanisms (such as those involvinginsulin receptor substrate 1) to indirectly enhance AMPK action,or some combination thereof.

• Pharmazeutische Anwendungen

  The biguanides proguanil and chlorproguanil are prodrugs, metabolized in vivo to the triazines cycloguanil and chlorcycloguanil, which have much enhanced activity in malaria treatment. Along with the diaminopyrimidines , they are often referred to as antifolates due to their mechanism of action. Proguanil is also used in combination with atovaquone, but the interaction has a different basis; antifolates do not enhance the effect of atovaquone.