CHARACTERIZATION OF ACETYLCHOLINESTERASE INHIBITION BY ITOPRIDE

Itopride is a gastroprokinetic benzamide derivative. This agent inhibi ted both electric eel acetylcholinesterase (AChE) and horse serum buty rylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04+/-0.27 mu M) was, however, 100-fold less than that with BuChE, whereas in th e case of neostigmine with AChE (11.3+/-3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was pa rtial, but that inhibited by upto 3 x 10(-5) M itopride was complete w hen the reaction mixture was subjected to ultrafiltration. Double reci procal plots of the experimental data showed that both K-m and V-max w ere affected by itopride, suggesting that the inhibition is a ''mixed' ' type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gast rointestine was much weaker than that on pure AChE. However, in the pr esence of a low dose of diisopropyl fluorophosphate, just enough to in hibit BuChE but not AChE, the IC(50)s of itopride against ChE activiti es were found to be about 0.5 mu M. In conclusion, itopride exerts rev ersible and a ''mixed'' type of inhibition preferably against AChE. Th e IC50 of itopride for electric eel and guinea pig gastrointestinal AC hE inhibition was 200 times and 50 times as large as that of neostigmi ne, respectively.