Home
Resources
Publications
A Colon-Specific Prodrug of Metoclopramide Ameliorates Colitis in an Experimental Rat Model

A Colon-Specific Prodrug of Metoclopramide Ameliorates Colitis in an Experimental Rat Model

Yejin Yang, Wooseong Kim, Dayoon Kim, Seongkeun Jeong, Jin-Wook Yoo, Yunjin Jung

Drug Des Devel Ther. 2018 Dec 28;13:231-242.

PMID: 30643389

Abstract:

Background:
We examined whether metoclopramide (MCP), a modulator of dopamine and serotonin receptors, alleviated colitis and had synergistic effects when coadministered with 5-aminosalicylic acid (5-ASA) in an experimental model of colitis.
Methods:
MCP azo-linked to 5-ASA (5-[4-chloro-2-{2-(diethylamino)ethylcarbamoyl}- 1-methoxyphenyl]azosalicylic acid, MCP-azo-ASA) was synthesized, where 5-ASA was used as a colon-targeting carrier and an anti-colitic agent, and the ability of MCP-azo-ASA to target the colon in vitro and in vivo was evaluated.
Results:
Our results indicate that MCP-azo-ASA was cleaved to MCP and 5-ASA in the cecal contents, but not in the contents of the small intestine. Oral gavage with equimolar concentrations of MCP-azo-ASA and sulfasalazine (SSZ, a colon-specific prodrug of 5-ASA widely used clinically) demonstrated that the two prodrugs delivered comparable amounts of 5-ASA to the cecum. MCP was barely detected in the blood after oral gavage with MCP-azo-ASA. In a rat model of 2,4-dinitrobenzene sulfonic acid hydrate (DNBS)-induced colitis, MCP-azo-ASA alleviated colonic damage in a dose-dependent manner. Moreover, MCP-azo-ASA reduced the concentrations of inflammatory mediators in the inflamed colon. At low equimolar doses, MCP-azo-ASA, but not SSZ, resulted in significant anti-colitic effects, which indicates that MCP has anti-colitic activity. MCP-azo-ASA had anti-colitic effects equal to those of SSZ at high equimolar doses.
Conclusion:
Thus, our results indicate that MCP-azo-ASA is a colon-specific prodrug of MCP. Targeted delivery of MCP to the colon ameliorated DNBS-induced colitis in rats, and we did not observe any synergistic effects of MCP after co-delivery with 5-ASA.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP1072952501	3-methoxypyridine-4-boronic acid hydrate	1072952-50-1	Price
LS7931156	1H-Pyrazol-3-ylboronic acid hydrate		Price
LS7931278	2-chloro-3-fluoropyridine-4-boronic acid hydrate		Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: