T-330

The effect of 2-[(2-dimethylaminobenzyl)sulfinyl]-1-(3-methylpyridine-2-yl)imidazole (T-330), on rat gastric H+/K+-ATPase was studied in vitro and in vivo in comparison with the irreversible proton pump inhibitor omeprazole. T-330 and omeprazole inhibited rat gastric H+/K+-ATPase at pH 6.1, and their IC50 values were 75 microM and 4.6 microM, respectively. Recovery from the T-330-inhibited H+K/+-AtPase activity was effected by beta-mercaptoethanol at concentrations above 10 microM, whereas significant recovery from the inhibition by omeprazole required 100 mM. When intraduodenally administered, T-330 (0.6-10 mg/kg) induced a more potent yet shorter-lasting inhibition of both gastric H+/K+ -ATPase activity and gastric acid secretion than did omeprazole (2.5-40 mg/kg). Recovery of the gastric H+/K+-ATPase activity depressed by omeprazole was completely blocked by an inhibitor of protein synthesis, cycloheximide, whereas that by T-330 was not prevented. This indicates that restoration of the enzyme activity after inhibition in vivo by T-330 does not require de novo synthesis of the enzyme in contrast to inhibition by omeprazole. beta-Mercaptoethanol (1 mM) fully restored the H+/K+-ATPase activity inhibited in vivo by T-330 but not by omeprazole. These observations indicate that T-330 reversibly inhibits gastric H+/K+-ATPase, resulting in a short-lasting antisecretory effect, and that the sulfhydryl groups of the enzyme are involved in the action of T-330.

Pre and postoperative metabolism of electrolytes and protein were studied in gastric cancer patients. Eight patients who underwent distal subtotal gastrectomy for gastric cancer, were treated with total parenteral nutrition (TPN) from the third day before surgery to the tenth day after surgery. Twelve patients who underwent total gastrectomy for gastric cancer were treated with enteral nutrition (EN, T-330, ED-AC) and TPN in the early postoperative phase. The results were as follows. 1) P which existed in intracellular space showed a decrease in the plasma level and a negative balance in the early postoperative phase. Thereafter, the plasma level of P ion increased and a positive balance was observed. 2) Ca showed a positive balance during the observation period. 3) The level of prealbumin and retinol-binding protein decreased to some extent after surgery, but came up to the preoperative level on the seventh postoperative day in enteral nutrition (T-330) after total gastrectomy. 4) Nitrogen balance was observed to show a positive balance on the seventh postoperative day. There was no statistical difference between the three groups. 5) There were significant relationships between the serum albumin level and the development of postoperative complications.