Inhibition of cholinesterase and acetylcholin-esterase in vitro by butyrophenone neuroleptics

Abstract

The inhibitory effect of six butyrophenone neuroleptics: haloperidol, triperidol, moperone, floropipamide, benperidol and droperidol on the activity of partially purified aspecific horse serum ChE and on purified Electrophorus electricus specific AChE was studied with AThCh as substrate using Ellman's spectrophotometric method. All butyrophenones were found to be inhibitors of ChE, the K i being in the range 10 −5 M and all followed a fully competitive type of inhibition. There were small differences in K i -values among various butyrophenones, while there were great differences in K i -values between the butyrophenones, the two phenothiazines and imipramine, the last three drugs being far more potent competitive ChE inhibitors ( K i 10 −6–10 −7 M) than the butyrophenones. All the butyrophenones were also found to inhibit AChE, the overall inhibitor constants being in the range 10 −4 to 10 −5 M and all showed a mixed type of inhibition. The most potent of the butyrophenones are droperidol and benperidol, the benzimidazolone derivatives. There are no great differences in the K i -values for the butyrophenones, the two phenothiazines and imipramine for inhibition of AChE.