Background:

IC50: 2.04 μM

Itopride is an acetylcholinesterase (AchE) inhibitor.

Acetylcholinesterase plays key roles in the termination of impulse transmission by rapidly hydrolyzing the neurotransmitter acetylcholine in varioius cholinergic pathways in both central and peripheral nervous systems.

In vitro: Itopride was found to inhibit both AChE and horse serum butyrylcholinesterase (BuChE). The itopride IC50 against AChE was, however, 100-fold less than that against BuChE. The recovery of AChE activity inhibited by low dose of neostigmine was partial, but that inhibited by itopride was complete. Double reciprocal plots showed that both Vmax and Km were affected by itopride, indicating a "mixed" type inhibition, although primarily being an uncompetitive one. In addition, the inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE [1].

In vivo: Previoius animal study showed that in conscious dogs with implanted strain gauge force transducers, itopride could stimulate contractile activity in the gastrointestinal tract from stomach to colon. Whereas, mosapride was able to stimulate contractile activity only in the gastric antrum and ileum. Moreover, in rats s andguinea pig, itopride could accelerate colonic luminal transit, however, both mosapride and cisapride failed to enhance colonic transit. Such findings suggested that itopride had a stimulatory action on propelling colonic luminal contents, colonic peristalsis, which was quite different from mosapride and cisapride [2].

Clinical trial: Itopride hydrochloride has been clinically used as a gastroprokinetic agent in several countries including Japan, for the symptomatic treatment of functional dyspepsia [2].

参考文献:
[1] Iwanaga Y,Kimura T,Miyashita N,Morikawa K,Nagata O,Itoh Z,Kondo Y.  Characterization of acetylcholinesterase-inhibition by itopride. Jpn J Pharmacol.1994 Nov;66(3):317-22.
[2] Tsubouchi T,Saito T,Mizutani F,Yamauchi T,Iwanaga Y.  Stimulatory action of itopride hydrochloride on colonic motor activity in vitro and in vivo. J Pharmacol Exp Ther.2003 Aug;306(2):787-93.