Inhibition of Human Blood Acetylcholinesterase and Butyrylcholinesterase by Ethopropazine

Inhibition of human erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7)and serum butyrylcholinesterase (BChE; EC 3.1.1.8)by ethopropazine, 10-(2-diethylaminopropyl)phenothiazine hydrochloride, was measured with acetylthiocholine (ATCh) as substrate.Dissociation constants for the enzyme-inhibitor complexes were calculated from the effect of ATCh concentration on the apparent dissociation constants by applying non-linear regression to fit the model to experimental data.Inhibition of AChE revealed a competitive inhibition for two binding sites (K a = 161 and K i = 393 mmol dm -3 ), inhibition of the atypical BChE was non-competitive (K i = 7.5 mmol dm -3 ) while that of the usual BChE was competitive (K (I) = 0.16 mmol dm -3 ).At the ethopropazine concentration of 20 mmol dm -3 and the acetylthiocholine concentration of 1.0 mmol dm -3 (conditions used for differentiation between AChE and BChE activities), the erythrocyte AChE was 8% inhibited and the BChE phenotypes UU, UA, FF/FS, AF, AJ/AK and AA/AS between 98% and 74%.