Kutovyi Y. The ability of imidazo[1,2-a]azepine derivatives for myocardium preconditioning

This work is based on experimental research of cardioprotective compounds among 9 imidazo[1,2-a]azepine derivatives. After screening experiments on isolated rat heart model we had chosen 2 the most active compounds in sense of preconditioning. Chosen compounds, namely IFT_000280 and IFT_000281 increased LVDP on 78 and 43% respectively and do not affect heart rate. Besides they increased coronary flow (on 51 and 38% respectively) and time of isolated heart contractions (on 39 and 32% respectively). Using ATP-dependent potassium channels blocker, glibenclamide, we have proved that imidazo[1,2-a]azepine derivative IFT_000281 acts on this type of channels what may induce its pharmacological effects. Selected compounds decreased creatine kinase and lactate dehydrogenase activity in heart effluent upon ischemia and reperfusion (on 10 and 15% for IFT_000280 and on 34% and 24% for IFT_000281 respectively).Compound IFT_000281 had decreased area of necrosis in experimental rats in vivo on 21% compared to control animals.