A novel orally administered trimebutine compound (GIC-1001) is anti-nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide-releasing capacity in mice

  • Eur J Pain. 2016 May;20(5):723-30. doi: 10.1002/ejp.798.
N Cenac  1  2  3 ,  M Castro  1  2  3 ,  C Desormeaux  1  2  3 ,  P Colin  4 ,  M Sie  1  2  3 ,  M Ranger  4 ,  N Vergnolle  1  2  3  5
Affiliations
  • 1. INSERM U1043, Toulouse, France.
  • 2. CNRS U5282, Toulouse, France.
  • 3. Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France.
  • 4. GIcare pharma Inc, Montréal, Canada.
  • 5. Department of Physiology and Pharmacology, University of Calgary, Canada.
PMID: 26541237 DOI: 10.1002/ejp.798
Abstract

Background: Trimebutine maleate, a noncompetitive spasmolytic agent with some affinity for peripheral μ- and κ-opioid receptors has been evaluated as a treatment in a limited number of patients undergoing sedation-free full colonoscopy. The efficiency of such treatment was comparable to sedation-based colonoscopies to relieve from pain and discomfort.

Methods: A new and improved trimebutine salt capable of releasing in vivo hydrogen sulphide (H2S), a gaseous mediator known to reduce nociception, has been developed. This drug salt (GIC-1001) is composed of trimebutine bearing a H2S-releasing counterion (3-thiocarbamoylbenzoate, 3TCB), the latter having the ability to release H2S. GIC-1001 has been tested here in a mouse model of colorectal distension.

Results: In mice, while orally given trimebutine (the maleate salt, non-H2 S-releaser) only slightly reduced the nociceptive response to increasing pressures of colorectal distension, oral administration of GIC-1001 (the H2S-releaser) was able to significantly reduce nociceptive response to all noxious stimuli, in a dose-dependent manner. This effect of GIC-1001 was significantly better than the effects of its parent compound trimebutine administered at equimolar doses.

Conclusions: Taken together, these results demonstrated increased antinociceptive properties for GIC-1001 compared to trimebutine, suggesting that this compound would be a better option to relieve from visceral pain and discomfort induced by lumenal distension.

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