Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 4, pp 435–444 | Cite as

Novel derivatives of 1,2,3-triazole, cannabinoid-1 receptor ligands modulate gastrointestinal motility in mice

  • Agata Szymaszkiewicz
  • Marta Zielinska
  • Kun Li
  • Mani Ramanathan
  • Safiul Alam
  • Duen-Ren Hou
  • Jakub Fichna
  • Martin Storr
Original Article


Cannabinoid-1 (CB1) receptors are broadly distributed in the central and peripheral nervous systems; among others, they are located in the enteric nervous system. In the gastrointestinal (GI) system, they participate in regulation of intestinal motility or ion transport. The aim of our study was to assess the effect of 1,2,3-triazole derivatives (compound 1: 2-[4,5-bis(2,4-dichlorophenyl)-2H-1,2,3-triazol-2-yl]-N-(2-fluorobenzyl)acetamide, compound 2: 2-[4,5-bis(2,4-dichlorophenyl)-2H-1,2,3-triazol-2-yl]-N-(4-fluorobenzyl)acetamide, compound 3: N-benzyl-2-[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2H-1,2,3-triazol-2-yl]acetamide]), characterized in vitro as CB1 antagonists with high CB1 over CB2 selectivity, in the mouse GI tract. The action of compounds 1–3 was assessed in vitro (electrical field stimulated smooth muscle contractility of the mouse ileum and colon) and in vivo (whole GI transit time). Compound 1 decreased ileal (10−6 M) and colonic (10−7–10−6 M) smooth muscles contractility. Moreover, it prolonged whole GI transit. Compound 2 (10−10–10−8 M) slightly increased the amplitude of muscle contractions in the ileum, but at a higher concentration (10−6 M), the amplitude was decreased. Compound 2 reduced colonic contractility but accelerated GI transit. Compound 3 decreased the amplitude of intestinal muscle contractions in the ileum (10−6 M) and colon (10−10–10−6 M). Moreover, it increased the GI transit time in vivo. Triazole derivatives possess easily modifiable structure and interesting pharmacological action in the GI tract; further, alterations may enhance their efficacy at CB receptors and provide low side effect profile in clinical conditions.


1,2,3-Triazoles Cannabinoid receptor CB1 antagonist SR141716A Rimonabant 


Author contributions

Designed the research study: JF, MS, DRH

Performed the research: JF, KL, MR, SA

Analyzed the data: JF, KL, AS, MZ

Wrote the paper: AS, MZ, JF, MS

All authors approved the final version of the manuscript.

Funding information

This study was supported by grants from the Medical University of Lodz (#503/1-156-04/503-01 to JF and 502-03/1-156-04/502-14-297 to MZ), grants from National Science Centre (#UMO-2014/13/B/NZ4/01179 to JF, #UMO-2013/11/N/NZ7/00724 and UMO-2014/12/T/NZ7/00252 to MZ), and grant from Ministry of Science and Higher Education (Iuventus Plus 5 Program #IP2015 089474 to MZ). AS and MZ are recipients of the Polish L’Oréal UNESCO Awards for Women in Science.

Compliance with ethical standards

All procedures used in this study were performed in accordance with respective national guidelines and approved by the Local Ethical Committee (protocol number #M07102).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Agata Szymaszkiewicz
    • 1
  • Marta Zielinska
    • 1
  • Kun Li
    • 2
  • Mani Ramanathan
    • 3
  • Safiul Alam
    • 3
  • Duen-Ren Hou
    • 3
  • Jakub Fichna
    • 1
  • Martin Storr
    • 2
    • 4
    • 5
    • 6
  1. 1.Department of Biochemistry, Faculty of MedicineMedical University of LodzLodzPoland
  2. 2.Snyder Institute for Chronic Diseases, Division of Gastroenterology, Department of MedicineUniversity of CalgaryCalgaryCanada
  3. 3.Department of ChemistryNational Central UniversityJhongli CityTaiwan
  4. 4.Walter Brendel Center of Experimental MedicineLudwig Maximilians University MunichMunichGermany
  5. 5.Center of EndoscopyStarnbergGermany
  6. 6.Department of Medicine, Division of GastroenterologyLudwig Maximilians University of MunichMunichGermany

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