In vitroreactivation of trichlorfon-inhibited butyrylcholinesterase using HI-6, obidoxime, pralidoxime and K048

Abstract

Trichlorfon is a specific inhibitor of cholinesterases. It was typically used as an insecticide; however, trichlorfon was described as useful for symptomatic treatment of Alzheimer's disease some years ago. The presented study is aimed at reactivation of trichlorfon-inhibited butyrylcholinesterase since this enzyme play an important role in Alzheimer's disease as deputy for acetylcholinesterase and furthermore it could be applied as a scavenger in case of overdosing. We used in vitro reactivation test for considering only reactivation efficacy of butyrylcholinesterase that is inhibited by trichlorfon and not reactivation of butyrylcholinesterase inhibited by trichlorfon metabolic products. Four reactivators were used: HI-6, pralidoxime, obidoxime, and K048. Although all of the reactivators seem to be effective at 1 mM concentration, a lower concentration was not able ensure sufficient reactivation. There was also an observed lowering of reactivation efficacy when butyrylcholinesterase was exposed to trichlorfon for a longer time interval.

Assessment of Acetylcholinesterase Activity Using Indoxylacetate and Comparison with the Standard Ellman’s Method

“…It could be a valuable alternative to the assay protocols based on Ellman’s method [23–25]. Pharmacological testing of anticholinersterase acting compounds is frequently based on blood AChE assay [13].…”

Oxime K027: novel low-toxic candidate for the universal reactivator of nerve agent- and pesticide-inhibited acetylcholinesterase

“…To elucidate its broad-spectrum potency, further investigations should be conducted, especially on human tissue. Moreover, its potency should be compared with results obtained recently with other oximes [42][43][44][45][46] . The present results point to the development of new oximes, which could enrich the group of current commercially available reactivators.…”

Acetylcholinesterase activity in Toxoplasma gondii tachyzoites (RH strain)

“…Although the enzyme AChE can be described in the genome of the T. gondii ME-49 strain (Lorenzi et al 2008), the AChE activity in parasite has not been studied and not explored in chemotherapy. Regarding to AChE inhibition, as all organophosphate insecticides, trichlorfon (also called metrifonate) acts on the nervous system of the parasites (but also of mammals, birds, fish, and many other organisms) providing an inhibition of AChE activity (Pohanka et al 2009). Thus, the aim of this study was to investigate the presence and the activity of enzyme AChE in T. gondii tachyzoites as well as to test some known inhibitor of this enzyme.…”