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

Novel derivatives of 1,2,3-triazole, cannabinoid-1 receptor ligands modulate gastrointestinal... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Naunyn-Schmiedeberg's Archives of Pharmacology Springer Journals

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

Loading next page...
 
/lp/springer_journal/novel-derivatives-of-1-2-3-triazole-cannabinoid-1-receptor-ligands-sBH9y1H1OS
Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Biomedicine; Pharmacology/Toxicology; Neurosciences
ISSN
0028-1298
eISSN
1432-1912
D.O.I.
10.1007/s00210-018-1465-9
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Naunyn-Schmiedeberg's Archives of PharmacologySpringer Journals

Published: Feb 5, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off