{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:22:52Z","timestamp":1789950172762,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T00:00:00Z","timestamp":1446768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"GICare pharma Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Trimebutine maleate, a noncompetitive spasmolytic agent with some affinity for peripheral \u03bc\u2010 and \u03ba\u2010opioid receptors has been evaluated as a treatment in a limited number of patients undergoing sedation\u2010free full colonoscopy. The efficiency of such treatment was comparable to sedation\u2010based colonoscopies to relieve from pain and discomfort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A new and improved trimebutine salt capable of releasing<jats:italic>in\u00a0vivo<\/jats:italic>hydrogen sulphide (H<jats:sub>2<\/jats:sub>S), a gaseous mediator known to reduce nociception, has been developed. This drug salt (<jats:styled-content style=\"fixed-case\">GIC<\/jats:styled-content>\u20101001) is composed of trimebutine bearing a H<jats:sub>2<\/jats:sub>S\u2010releasing counterion (3\u2010thiocarbamoylbenzoate, 3<jats:styled-content style=\"fixed-case\">TCB<\/jats:styled-content>), the latter having the ability to release H<jats:sub>2<\/jats:sub>S.<jats:styled-content style=\"fixed-case\">GIC<\/jats:styled-content>\u20101001 has been tested here in a mouse model of colorectal distension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In mice, while orally given trimebutine (the maleate salt, non\u2010H<jats:sub>2<\/jats:sub>S\u2010releaser) only slightly reduced the nociceptive response to increasing pressures of colorectal distension, oral administration of<jats:styled-content style=\"fixed-case\">GIC<\/jats:styled-content>\u20101001 (the H<jats:sub>2<\/jats:sub>S\u2010releaser) was able to significantly reduce nociceptive response to all noxious stimuli, in a dose\u2010dependent manner. This effect of<jats:styled-content style=\"fixed-case\">GIC<\/jats:styled-content>\u20101001 was significantly better than the effects of its parent compound trimebutine administered at equimolar doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these results demonstrated increased antinociceptive properties for<jats:styled-content style=\"fixed-case\">GIC<\/jats:styled-content>\u20101001 compared to trimebutine, suggesting that this compound would be a better option to relieve from visceral pain and discomfort induced by lumenal distension.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.798","type":"journal-article","created":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T09:14:41Z","timestamp":1446801281000},"page":"723-730","source":"Crossref","is-referenced-by-count":41,"title":["A novel orally administered trimebutine compound (<scp>GIC<\/scp>\u20101001) is anti\u2010nociceptive and features peripheral opioid agonistic activity and 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