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

作者：Cenac N; Castro M; Desormeaux C; Colin P; Sie M; Ranger M; Vergnolle N^*

来源：European Journal of Pain, 2016, 20(5): 723-730.

DOI：10.1002/ejp.798

BackgroundTrimebutine maleate, a noncompetitive spasmolytic agent with some affinity for peripheral - and -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.
MethodsA new and improved trimebutine salt capable of releasing invivo 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.
ResultsIn mice, while orally given trimebutine (the maleate salt, non-H2S-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.
ConclusionsTaken 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.

• 出版日期2016-5