Influence of trimebutine on inflammation- and stress-induced hyperalgesia to rectal distension in rats.
The effects of trimebutine and its major metabolite, N-desmethyltrimebutine on inflammation- and stress-induced rectal hyperalgesia have been evaluated in rats fitted with electrodes implanted in the longitudinal striated muscle of the abdomen. Intermittent rectal distension was performed before and 3 days after induction of rectal inflammation by local infusion of trinitrobenzenesulphonic acid (in ethanol). Stress consisted of 2h partial restraint and rectal distension was performed before and 30min after the end of the partial restraint session. The animals were treated intraperitoneally with trimebutine or desmethyltrimebutine (5, 10 or 20mgkg(-1)) or vehicle 15min before rectal distension. Naloxone (1mgkg(-1)) or saline was injected subcutaneously before trimebutine and desmethyltrimebutine. Before treatment trimebutine at the highest dose (20mgkg(-1)) reduced the abdominal response to rectal distension for the highest volume of distension (1.6mL) whereas desmethyltrimebutine was inactive. After rectocolitis the abdominal response to rectal distension was enhanced and trimebutine at 5mgkg(-1) reduced and at 10 mgkg(-1) suppressed inflammation-induced hyperalgesia, an effect reversed by naloxone. Desmethyltrimebutine was inactive. Stress-induced hypersensitivity was attenuated or suppressed, or both, by trimebutine and desmethyltrimebutine at doses of 5, 10 or 20mgkg(-l); greater efficacy was observed for desmethyltrimebutine and the effects were not reversed by naloxone. It was concluded that trimebutine and desmethyltrimebutine are active against inflammation- and stress-induced rectal hyperalgesia but act differently. The effect of trimebutine on inflammation-induced hyperalgesia is mediated through opioid receptors.
Lacheze
C
C
Department of Pharmacology, INRA, Toulouse, France.
Coelho
A M
AM
Fioramonti
J
J
Buéno
L
L
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D010529:Peritoneal Cavity; D011349:Proctitis / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects; D012007:Rectum / Q000187:drug effects* / Q000503:physiopathology*; D012149:Restraint, Physical; D014287:Trimebutine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D011957:Receptors, Opioid; C053065:N-desmethyltrimebutine; D014302:Trinitrobenzenesulfonic Acid; D014287:Trimebutine