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-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.

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.

from European Journal of Pain http://ift.tt/1SuRN0I
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