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Effect of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl] propionic acid hydrochloride on gastric mucosa directly from the lumen.

The present experiments were designed to determine if the novel anti-ulcer drug 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid hydrochloride (TEI-5103, TG-51), acts on the gastric mucosa directly from the lumen when given orally. TEI-5103 given orally (50-400 mg/kg) prevented the lesion formation induced by 0.1N HCl + 60% ethanol, but when given intraperitoneally (50-200 mg/kg) or intravenously (40 mg/kg), it did not prevent the formation of lesions. Indomethacin-induced gastric lesions were inhibited by oral administration of TEI-5103, but not by intraduodenal administration. In pylorus-ligated rats, TEI-5103 given intragastrically also inhibited the development of gastric lesions induced by HCl + ethanol. These results suggest that the presence of TEI-5103 in the stomach is necessary to elicit its anti-ulcer effect. In microautoradiographic examination, silver grains corresponding to [14C]-TEI-5103 distributed in the upper part of the mucosa (luminal side) at 0.5 to 4 h after the oral administration. However, when given intraduodenally or intravenously, this high concentration of [14C]-TEI-5103 was not observed in the stomach tissue. When given orally, the content of [14C]-TEI-5103 in rat stomach tissue was about 100 times higher than that in plasma and the time course of distribution was different from that seen in the gastric content. From these results, it seems that TEI-5103 distributes in the gastric mucosa directly from the lumen. In conclusion, TEI-5103, when given orally, distributes in the gastric mucosa as a target issue directly from the lumen; and only the oral and gastric route of administration lead to the anti-ulcer effect.