Figure 5.

Enzyme inhibition kinetic analysis of duloxetine against human butyrylcholinesterase. (A) Duloxetine acts as a potent inhibitor of human BChE with a competitive mode of action. Nonlinear regression analyses estimated an inhibition constant (K_i) of 351 nM for duloxetine against human BChE. (B) Similar nonlinear regression analyses indicate that physostigmine, a well-known nonselective cholinesterase inhibitor, has in comparison to duloxetine over 2-folds less affinity for human plasma BChE, as it can be deduced by a K_i value of 844 nM. (C) Ethopropazine, a well-known, highly potent, and selective BChE inhibitor, exhibits a K_i value of 150 nM in similar analyses in our laboratory. A comparison of the K_i value of ethopropazine with that of duloxetine indicates that duloxetine is indeed a potent inhibitor of human plasma BChE. (D, E) Nonlinear regression analyses indicated that in contrast to duloxetine, citalopram and its pure enantiomer, escitalopram, were much weaker BChE inhibitors, as is deduced by their estimated K_i of 42 and 203 μM against human BChE, respectively. The nonlinear regression analyses were done with GraphPad Prism 9. Data are given as mean ± SD.