Kinetics of human erythrocyte acetylcholinesterase inhibition by a novel derivative of physostigmine: Phenserine

The effect of phenserine, a novel cholinesterase inhibitor, was assessed for the first time on kinetic parameters of human erythrocyte acetylcholinesterase (AChE). Phenserine (0.025-0.40 mu M) inhibited the activity of human erythrocyte AChE in a concentration-dependent fashion, the IC50 was 0.0453 mu M. The Michaelis-Menten constant (K-m) for the hydrolysis of acetylthiocholine iodide was found to be 0.124 mM and the V-max was 0.980 mu mol/min/mg protein. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the noncompetitive type. The value of K-i was estimated as 0.048 mu M by the primary and secondary replots of the Dixon as well as secondary replots of the Line Neaver-Burk plot. A novel relationship between K-i and substrate concentration was also identified which permits more precise prediction of the specific type of noncompetitive inhibition of various enzymes by a wide variety of drugs, chemicals and, in some circumstances, by their own substrates. (C) 1998 Academic Press.