In vitro effects of acetylcholinesterase inhibitors and reactivators on Complex I of electron transport chain.

OBJECTIVES

Inhibition of the enzyme acetylcholinesterase (AChE) is the main mechanism both of therapeutic action of drugs for the treatment of Alzheimer's disease and toxic action of organophosphorus compounds. Various types of oximes reactivate AChE and are commonly used as antidotes against organophosphates (pesticides, nerve agents).

METHODS

Effects both of AChE inhibitors (tacrine, 7-methoxytacrine) and oximes (pralidoxime, trimedoxime, obidoxime, methoxime, HI-6) on Complex I of electron transport chain (ETC) were examined. The enzyme activity was measured spectrophotometrically in crude mitochondrial fraction isolated from pig brain.

RESULTS

Our results showed statistically significant Complex I inhibition by tacrine, other drugs did not affect the enzyme activity significantly.

CONCLUSIONS

These observations suggest the possibility of tacrine-induced side effects related to disturbance in ETC. On the contrary, it seems that oximes do not affect cellular energetic metabolism.