| 18763029 |
Zoccarato F, Cappellotto M, Alexandre A: Clorgyline and other propargylamine derivatives as inhibitors of succinate-dependent H (2) O (2) release at NADH:UBIQUINONE oxidoreductase (Complex I) in brain mitochondria. Bioorg Med Chem Lett. 2003 Nov 17;13(22):4101-5.
Complex I is the main O (2)(-) producer of the mitochondrial respiratory chain. O (2)(-) release is low with NAD-linked substrates and increases strongly during succinate oxidation, which increases the QH (2)/Q ratio and is rotenone sensitive. We show that the succinate dependent O (2)(-) production (measured as H (2) O (2) release) is inhibited by propargylamine containing compounds (clorgyline, CGP 3466B, rasagiline and TVP-1012). The inhibition does not affect membrane potential and is unaffected by DeltapH modifications. Mitochondrial respiration is similarly unaffected. The propargylamines inhibition of O (2)(-)/H (2) O (2) production is monitored also in the presence of the Parkinson's disease toxin dopaminochrome which stimulates O (2)(-) release. Propargylamine-containing compounds are the first pharmacological inhibitors described for O (2)(-) release at Complex I. |
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