Drug Delivery and Translational Research

, Volume 9, Issue 1, pp 334–343 | Cite as

Therapeutic switching of sulpiride, an anti-psychotic and prokinetic drug, to an anti-colitic drug using colon-specific drug delivery

  • Dohoon Kim
  • Wooseong Kim
  • Seongkeun Jeong
  • Dayoon Kim
  • Jin-Wook Yoo
  • Yunjin JungEmail author
Original Article


To test whether sulpiride (SP), an anti-psychotic and prokinetic drug, shows beneficial effects on experimental murine colitis, a colon-targeted prodrug of SP, 5-(aminoethanoylsulfamoyl)-N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxybenzamide (glycylsulpiride (GSP)), was synthesized and its colonic delivery and therapeutic activity against 2,4-dinitrobenzenesulfonic acid (DNBS)–induced rat colitis were assessed. Synthesis of GSP was verified by infrared and proton nuclear magnetic resonance spectroscopy. GSP was converted to SP when incubated with the cecal contents but not when incubated with the small intestinal contents. The percent conversion was about 50.5% at 6 h and 67.7% at 10 h. Colonic delivery of GSP was examined by comparison with sulfasalazine (SSZ), a colon-specific prodrug of 5-aminosalicylic acid currently used for the treatment of inflammatory bowel disease. The two prodrugs accumulated similar concentrations of the corresponding parent drugs in the cecum at 2, 4, and 6 h after oral gavage. Although oral gavage of GSP released millimolar level of SP in the large intestine, SP was hardly detected in the blood. GSP improved colonic damage score and reduced myeloperoxidase activity up to 80.5% in the inflamed colon in a dose-dependent manner. Moreover, GSP was able to reduce the levels of inflammatory mediators in the inflamed colon. Overall, the anti-colitic effectiveness of GSP and SSZ was similar. In conclusion, colonic delivery of SP ameliorates DNBS-induced colitis in rats with no significant systemic absorption of SP. Thus, colon-targeted SP may be therapeutically switched to an anti-colitic drug.


Sulpiride Dopamine antagonist Colonic delivery Prodrug Colitis Therapeutic switching 


Funding information

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A3B07045694).

Compliance with ethical standards

The animal protocol used in this study was reviewed and approved by the Pusan National University—Institutional Animal Care and Use Committee (Approval number: PNU-2017-1525; Approval date: 2017-04-19) for ethical procedures and scientific care. All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13346_2018_599_MOESM1_ESM.pdf (434 kb)
ESM 1 (PDF 434 kb)


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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  • Dohoon Kim
    • 1
  • Wooseong Kim
    • 1
  • Seongkeun Jeong
    • 1
  • Dayoon Kim
    • 1
  • Jin-Wook Yoo
    • 1
  • Yunjin Jung
    • 1
    Email author
  1. 1.College of PharmacyPusan National UniversityPusanRepublic of Korea

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