Metformin Hydrochloride
Pharmacology
Metformin Hydrochloride is the hydrochloride salt of the biguanide metformin with antihyperglycemic and potential antineoplastic activities. Metformin inhibits complex I (NADPH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, thereby increasing the cellular AMP to ATP ratio and leading to activation of AMP-activated protein kinase (AMPK) and regulating AMPK-mediated transcription of target genes. This eventually prevents hepatic gluconeogenesis, enhances insulin sensitivity and fatty acid oxidation and ultimately leads to a decrease in glucose levels. Metformin may exert antineoplastic effects through AMPK-mediated or AMPK-independent inhibition of mammalian target of rapamycin (mTOR), which is up-regulated in many cancer tissues. Furthermore, this agent also inhibits tumor cell migration and invasion by inhibiting matrix metalloproteinase-9 (MMP-9) expression which is mediated through the suppression of transcription activator protein-1 (AP-1) activation.
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