Butyrylcholinesterase inhibition

Most insecticides, especially the organophosphate group, cause neurotoxicity as their major mode of action. Assessment of the neurotoxicity includes neurochemical endpoints such as cholinesterase (including acetylcholinesterase, which is the major neurotransmitter in vertebrates such as fish, and other enzymes such as butyrylcholinesterase) inhibition and behavioral endpoints such as swimming speed [79]. Studies done in rats show the neurotoxic action of insecticides such as dimethoate, methyl parathion, dichlorvos, ethyl parathion or propoxur after a prolonged exposure [80,81]. 

Attar-ur-Rahman A, ParveenS, Khalid A, et al., Acev/X- and butyrylcholinesterase inhibiting triterpenoids from Buxus papillosa, Phytochemistry 58 963—968, 2001. 

Nachon F, Asojo OA, Borgstahl G, Masson P, Lockridge O (2005) Role of water in aging of human butyrylcholinesterase inhibited by echothiophate the crystal structure suggests two alternative mechanisms of aging, Biochemistry 44 1154-1162... 

Theoretically, butyrylcholinesterase inhibition centrally could enhance therapeutic efficacy... 

Theoretically, butyrylcholinesterase inhibition peripherally could enhance side effects... 

Sun, J., Lynn, B.C. (2007). Development of a MALDI-TOF-MS method to identify and quantify butyrylcholinesterase inhibition resulting from exposure to organophosphate and carbamate pesticides. J. Am. Soc. Mass Spectrom. 18 698-706. 

The synthesis, toxicity, neuroprotection, and human acetyl-cholinesterase/butyrylcholinesterase inhibition properties of ft-naphthotacrinesl-14 have been reported [176]. p-Naphthotacrines 1-14 showed lower toxicity than tacrine. 

Novel resveratrol derivatives (polyhydroxylated (E)-stilbenes), synthesized by Mizoroki-Heck reactions, revealed potent butyrylcholinesterase-inhibiting properties [225]. 

Schaper derived equations to describe the nonlinear dependence of the biological activities of racemates at different concentrations on the activities of the pure enantiomers [875]. Not only quantitative but also qualitative differences were observed for the QSARs of different enantiomers of chiral phosphonic acids a linear dependence of butyrylcholinesterase inhibition on chain length resulted for the ( + ) enantiomers, while a clear bilinear dependence was observed for the (—) isomers [876]. 

Kamal MA, Klein P, Luo W, Li Y, Holloway HW, Tweedie D, Greig NH (2008) Kinetics of human serum butyrylcholinesterase inhibition by a novel experimental Alzheimer therapeutic, dihydrobenzodioxepine cymserine. Neurochem Res 33 745-753... 

Jun, D., Musilova, L., Lazenska, H., et al., 2007. Potency of several oximes to reactivate human acetylcholinesterase and butyrylcholinesterase inhibited by paraoxon and methyl-paraoxon in vitro. The IXth International Meeting on Cholinesterases. Suzhou, China, May 6-10, 2007. Program Book, p. 140. 

E. Carletti, N. Aurbek, E. Gillon, M. Loiodiee, Y. Nicolet, J. C. Fontecil-la-Camps, P. Masson, H. Thiermann, F. Naehon and F. Worek, Structure-activity analysis of aging and reactivation of human butyrylcholinesterase inhibited by analogues of tabun, Biochem.J, 2009,421,97-106. 

---