We have evaluated the potential protective activity of
nepadutant, a selective
tachykinin NK2 receptor antagonist, in a model of acute
rectocolitis induced by an
enema with 7.5%
acetic acid in guinea-pigs. The injury was quantified visually by using a macroscopic injury score, and histologically by using a
necrosis score. In addition, changes in
myeloperoxidase activity, a marker for neutrophil infiltration, and
plasma protein extravasation were evaluated. The injury caused by 7.5%
acetic acid was mild, affecting the superficial layers and producing a strong
edema of the submucosa. A single administration of
nepadutant (0.3-10 mg/kg s.c., 1 h before
acetic acid) markedly reduced the macroscopic damage and
necrosis score and the increase in
plasma protein extravasation induced by 7.5%
acetic acid in the early phase of the injury. Single administration of
nepadutant (3 mg/kg s.c.) reduced the macroscopic score and
myeloperoxidase activity at the top (24 h) of
inflammation. Repeated administration (3 mg/kg s.c. three times during 24 h) or co-administration of the
tachykinin NK1 receptor antagonist
MEN 11467 (3 mg/kg s.c.) did not enhance the antiulcer effect obtained with the single treatment with
nepadutant. These data suggest the involvement of
tachykinin NK2 receptors in the first phases of
inflammation induced by
acetic acid.