aicar peptides

Aicar peptides, also known as ZMP, is an intermediate in the generation of inosine monophosphate. Aicar peptide is an analog of adenosine monophosphate (AMP). And it is capable of stimulating AMP-dependent protein kinase (AMPK) activity. Doctors have already used Aicar clinically to treat and protect against cardiac ischemic injury. In the 1980s, doctors have already used the drug as a method to preserve blood flow to the heart during surgery.

Currently, it was shown that Aicar as a potential treatment for diabetes by increasing the metabolic activity of tissues by changing the physical composition of muscle. AICAR (commonly under the name Acadesine) is an analog of adenosine. It enters cardiac cells to inhibit adenosine kinase and adenosine deaminase. It enhances the rate of nucleotide re-synthesis increasing adenosine generation from adenosine monophosphate only during conditions of myocardial ischemia. In cardiac myocytes, AICA-riboside is phosphorylated to AICA-ribotide (ZMP) to activate AMPK without changing the levels of the nucleotides. ZMP is able to enter the de novo synthesis pathway for adenosine synthesis to inhibit adenosine deaminase causing an increase in ATP levels and adenosine levels.

AICAR has been shown to precondition the heart shortly before or during ischemia.

AICAR triggers a preconditioned anti-inflammatory state by increasing NO production from endothelial nitric oxide synthase.

When AICAR is given 24 hours prior to reperfusion, it prevents post ischemic leukocyte-endothelial cell adhesive interactions with increased NO production.

AICAR-dependent preconditioning is also mediated by an ATP-sensitive potassium channel and hemeoxygenase-dependent mechanism. It increases AMPK-dependent recruitment of ATP-sensitive K channels to the sarcolemma causing the action potential duration to shorten, and preventing calcium overload during reperfusion.

The decrease in calcium overload prevents inflammation activation by ROS.