The currently available experimental data supports the hypothesis that the 
neuroprotective effect of dimebon is related to the protection of the 
brain-mitochondria from neurodegeneration. In this study, the influence of 
dimebon on mitochondria was investigated to gain a better understanding of the 
neuroprotective effects of this drug. Here, we demonstrate that dimebon enhances 
the resistance of the isolated rat brain and liver mitochondria to the induction 
of mitochondrial permeability transition (MPT) by calcium ions even in the 
presence of atractyloside, a MPT pore (MPTP) opener, but is ineffective against 
atractyloside-induced mitochondria swelling. Unlike cyclosporine A (CsA), a MPTP 
inhibitor, Dimebon does not influence the adenine nucleotide translocase (ANT) 
conformational changes and is not able to prevent the MPT of de-energized 
mitochondria. Using three different assays, and using amyloid-β peptide for 
inducing mitochondrial toxicity, we show that the influence of dimebon on the 
calcium retention capacity (CRC) of mitochondria depends on the mode of calcium 
addition. No obvious influence of dimebon on CRC was observed under the 
conditions of calcium infusion in the pump mode but the increase of CRC of rat 
brain mitochondria was observed when calcium was added in the bolus mode; the 
addition of calcium in the single pulse mode led to the increase of the lag 
period of calcium efflux from mitochondria. From these studies it is shown that 
dimebon is effective against amyloid-β (Aβ) potentiated mitochondrial swelling 
and decrease of calcium retention capacity (CRC) of the brain mitochondria.