Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage.
The discovery that pyridoxamine (PM) can inhibit glycation reactions and the formation of advanced glycation end products (AGEs) stimulated new interest in this B6 vitamer as a prospective pharmacological agent for treatment of complications of diabetes. The mechanism of action of PM includes: (i) inhibition of AGE formation by blocking oxidative degradation of the Amadori intermediate of the Maillard reaction; (ii) scavenging of toxic carbonyl products of glucose and lipid degradation; and (iii) trapping of reactive oxygen species. The combination of these multiple activities along with PM safety posture it as a promising drug candidate for treatment of diabetic complications as well as other multifactorial chronic conditions in which oxidative reactions and carbonyl compounds confer pathogenicity.
Voziyan
P A
PA
Division of Nephrology, Vanderbilt University Medical Center, S-3223 MCN, 1161 21st Avenue South, Nashville, Tennessee 37232-2372, USA. paul.voziyan@vanderbilt.edu
Hudson
B G
BG
D000818:Animals; D048909:Diabetes Complications / Q000188:drug therapy / Q000209:etiology; D017127:Glycation End Products, Advanced / Q000096:biosynthesis*; D006801:Humans; D015416:Maillard Reaction; D018384:Oxidative Stress / Q000187:drug effects*; D011733:Pyridoxamine / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism
D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D011733:Pyridoxamine