Itopride hydrochloride Chemical Properties

Melting point:

194-1950C

storage temp. 

2-8°C

solubility 

H2O: ≥48mg/mL

form 

powder

color 

white to tan

Water Solubility 

H2O: ≥48mg/mL

λmax

258nm(MeOH)(lit.)

Merck 

14,5244

InChI

InChI=1S/C20H26N2O4.ClH/c1-22(2)11-12-26-17-8-5-15(6-9-17)14-21-20(23)16-7-10-18(24-3)19(13-16)25-4;/h5-10,13H,11-12,14H2,1-4H3,(H,21,23);1H

InChIKey

ZTOUXLLIPWWHSR-UHFFFAOYSA-N

SMILES

C1(C(=O)NCC2=CC=C(OCCN(C)C)C=C2)=CC=C(OC)C(OC)=C1.Cl

CAS DataBase Reference

122892-31-3(CAS DataBase Reference)

Safety Information

Hazard Codes 

N

Risk Statements 

50

Safety Statements 

61

RIDADR 

UN 3077 9 / PGIII

WGK Germany 

3

RTECS 

CV4552000

HS Code 

2924.29.7790

Itopride hydrochloride Usage And Synthesis

Description

Itopride, a gastroprokinetic benzamide derivative was launched in Japan for the relief of gastrointestinal symptoms in patients with chronic gastritis. ltopride is a dopamine D₂-receptor antagonist that stimulates acetylcholine (Ach) release on the postganglionic cholinergic neurons to cause Ach accumulation at muscarinic receptors and, therefore, enhances Ach-induced gastric contractions. In animal models, itopride was reported to increase GI transit and gastric emptying.

Chemical Properties

Crystalline Solid

Originator

Hokuriku (Japan)

Uses

Dopamine D2-receptor antagonist with anticholinesterase activity. Gastroprokinetic

Uses

Dopamine D2 receptor blockade,acetylcholinesterase inhibitor

Uses

Anti-Spasmodics

brand name

Ganaton

General Description

Itopride hydrochloride is a new prokinetic drug.

Biochem/physiol Actions

Itopride hydrochloride enhances the gastrointestinal motility by blocking the activity of dopamine on the D2 receptors, on the post-synaptic cholinergic nerves and by inducing the liberation of acetylcholine in the myenteric plexus. It also inhibits the hydrolysis of the released acetylcholine with the help of acetylcholinesterase.

Synthesis

The general procedure for the synthesis of N-(4-(2-(dimethylamino)ethoxy)benzyl)-3,4-dimethoxybenzamide hydrochloride using etopride as a raw material is as follows: 16 kg of dry etopride and 56 kg of sec-butanol from Example 4 were added to a reactor and heated to 50-55°C until completely dissolved. 4.8 kg of 37% hydrochloric acid solution was added slowly and dropwise, during which the pH of the reaction mixture was monitored to ensure that it was below 2.0. The reaction mixture was stirred continuously at 50-55°C for at least 30 minutes. The mixture was then cooled to 15-25 °C and centrifuged. The precipitate was washed with 16.0 kg of sec-butanol. Finally, the product was dried at 70-80 °C to obtain 16.5 kg of itopride hydrochloride with HPLC purity of more than 99.8%. The yield of the reaction was 93.7% compared to etopride.

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].

IC 50

2.04 μm

References

[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.

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