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Pharmacology of mitochondrial permeability transition pore inhibitors
Author(s) -
Naryzhnaya Natalia V.,
Maslov Leonid N.,
Oeltgen Peter R.
Publication year - 2019
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21593
Subject(s) - mitochondrial permeability transition pore , mptp , necroptosis , pharmacology , apoptosis , myocardial infarction , mitochondrion , reperfusion injury , chemistry , medicine , programmed cell death , ischemia , cardiology , biochemistry , disease , parkinson's disease
It is now firmly established that an important event in the formation of reperfusion injury of the heart is the opening of mitochondrial permeability transition pores (mPTPs), which changes the permeability of the mitochondria. mPTP opening results in the death of cardiomyocytes through activation of apoptosis and necroptosis. Experimental studies have shown that pharmacological inhibition of mPTP opening promotes the reduction in the infarct size and the suppression of apoptosis. Indeed, studies have shown the efficacy of mPTP inhibitors in animal models of myocardial reperfusion and isolated human myocardial trabeculae. However, clinical trials of cyclosporin A and TRO40303 have not provided a clear answer to the question of the effectiveness of mPTP inhibitors in patients with acute myocardial infarction. This article presents an analysis of possible approaches for the pharmacological regulation of mPTP during reperfusion injury of the heart.