title: In vitro effects of acetylcholinesterase inhibitors and reactivators on Complex I of electron transport chain.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry, 1st Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Hroudová
authors.forename: Zdenĕk
authors.initials: Z
authors.lastname: Fisar
authors.forename: Jan
authors.initials: J
authors.lastname: Korábečný
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuča
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects*; D045222:Electron Transport Chain Complex Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects; D042967:Electron Transport Complex I / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology; D013552:Swine; D013619:Tacrine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D045222:Electron Transport Chain Complex Proteins; D010091:Oximes; D013619:Tacrine; C016222:7-methoxytacrine; D042967:Electron Transport Complex I