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.