title: A novel orally administered trimebutine compound (GIC-1001) is anti-nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide-releasing capacity in mice.
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.
authors.affiliation: INSERM U1043, Toulouse, France.|CNRS U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France.
authors.forename: N
authors.initials: N
authors.lastname: Cenac
authors.affiliation: INSERM U1043, Toulouse, France.|CNRS U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France.
authors.forename: M
authors.initials: M
authors.lastname: Castro
authors.affiliation: INSERM U1043, Toulouse, France.|CNRS U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France.
authors.forename: C
authors.initials: C
authors.lastname: Desormeaux
authors.affiliation: GIcare pharma Inc, Montréal, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Colin
authors.affiliation: INSERM U1043, Toulouse, France.|CNRS U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France.
authors.forename: M
authors.initials: M
authors.lastname: Sie
authors.affiliation: GIcare pharma Inc, Montréal, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Ranger
authors.affiliation: INSERM U1043, Toulouse, France.|CNRS U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France.|Department of Physiology and Pharmacology, University of Calgary, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Vergnolle
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D003106:Colon; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000187:drug effects*; D011312:Pressure; D059265:Visceral Pain
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D001557:Benzenesulfonates; C000605012:trimebutine 3-thiocarbamoylbenzenesulfonate; D006862:Hydrogen Sulfide