Fig. 8.

Schematic drawing illustrating the potential mechanism of action of novel (hetero)arylalkenylpropargylamines (SZV) in the striatum. Mitochondrial deficit, caused by the mitochondrial complex I inhibitor rotenone leads to reactive oxygen species (ROS) generation. Coincident or subsequent oxidative stress, mimicked in our experiments by H₂O₂ leads to redistribution of DA from synaptic vesicles to cytoplasm, where it is converted to toxic dopamine quinone (DAQ). DA is then released to the extracellular space. DAQ targets the cysteinyl residues of peptides and proteins and compromise cellular function at multiple target sites and aggravates mitochondrial deficit. SZV compounds 1. inhibit MAO-B enzyme, and thereby increase the biological availability of dopamine; 2. in addition, they prevent oxidative stress induced pathological DA efflux and its further formation to toxic DAQ, independent from the inhibition of MAO-B, but do not have direct antioxidant property and do not influence physiological neuronal activity induced DA release, mimicked by electrical field stimulation (EFS)