In vitro kinetic study of donepezil N-oxide metabolites

Abstract EN

Objective : The aim of this study was to examine the metabolism of donepezil via N– oxidation of donepezil HCl in vitro, and the kinetic studies at a temperature similar to that of the human body.

Methods : Direct reaction of donepezil with hydrogen peroxide and formic acid at room temperature, the N–oxide undergoes a series of rearrangements, the reaction was followed by ultraviolet at λmax = 268 nm at 37 °C.

The donepezil N-oxide was also tested as potential cholinesterase inhibitor using electrometric for cholinesterase determination.

Results : According to the present work, the structure of donepzil N-oxide was elucidated using spectroscopic analysis, also, in vitro kinetic study at 37 °C using ultraviolet spectrophotometer at λmax = 268 nm showed that the reaction proceeded at a first order reaction.

Biologically, the compound was found to inhibit both plasma and erythrocyte cholinesterase activities in vitro .

Conclusion : We concluded that the N-oxide of denepezil undergoes a series of rearrangements, the reaction followed first order at 37 °C.

It has a potential anticholinesterase activity.