ABSTRACT-The effects of [1][2]fumarate, on the loperamide or clonidine-induced delayed propulsion were determined in rats and compared with those of other gastroprokinetic agents. Administration of loperamide (0.3 mg/kg, s.c.) or clonidine (0.01 mg/kg, s.c.) induced delay of the evacuation time of the teflon ball, which had been inserted into the distal colon. The delayed evacuation was improved dose dependently by KW-5092 at 3 to 10 mg/kg (p.o.) or higher. Neostigmine at 0.3 to 3 mg/kg (p.o.) and T-1815 at 1 to 100 mg/kg (p.o.) also improved the delayed ball evacuation. These results suggest that KW-5092 stimulates the delayed colonic propulsion.

No abstract

Abstract. The effects of orally administered dipeptidyl peptidase IV (DPP-IV) inhibitor on the glucose-lowering effect of glibenclamide are still unknown. We evaluated the effects of combination treatment with a long-lasting DPP-IV inhibitor, K579 ((S)-1-[4-methyl-1-(2-pyrimidinyl)-4-piperidylamino]acetyl-2-pyrrolidinecarbonitrile), and glibenclamide on the glycemic responses to glucose loading in rats. Treatment with K579 inhibited the plasma DPP-IV activity even 8 h after the administration. K579 significantly suppressed the blood glucose elevation in glibenclamide-pretreated rats without excessive hypoglycemia. These profiles of K579 indicate that it could be useful agent to correct the postprandial glucose excursion in type 2 diabetes patients by combination treatment with glibenclamide.

Cyclical motor activity of the gastrointestinal tract, normally occurring during the interdigestive period in several mammals, is disrupted in the post-operative ileus. We determined the recovery from the disappearance of cyclical motor activity, from the stomach to the colon, in dogs after laparotomy with the force transducers. Moreover, we examined the effects of Leu13-motilin (KW-5139) and prostaglandin F2 alpha (PGF2 alpha), administered in the early post-operative period, on the gastrointestinal motility. Following laparotomy, the cyclical motor activity reappeared firstly in the ileum and the colon, then in the jejunum and the duodenum, and finally in the stomach. The reappearance time of the phase III contractions in the stomach was 105.8 +/- 10.6 h (n = 4). In the early post-operative period, KW-5139 (0.5 microgram kg-1, i.v.) induced phase-III-like contractions, whereas PGF2 alpha (50 micrograms kg-1, i.v.) induced simultaneously occurring contractions over the whole gastrointestine. The treatment with KW-5139 (0.5 microgram kg-1, i.v.) four times (twice daily on the first and the second post-operative day) significantly (P < 0.05) shortened the time required to recover the phase III contractions in the stomach (64.2 +/- 2.2 h, n = 4), whereas that with PGF2 alpha (50 micrograms kg-1, i.v.) four times did not (111.3 +/- 17.2 h, n = 4). The present results indicate that, after laparotomy, the cyclical motor activity recovers faster in the distal intestine than in the proximal intestine and the stomach, and that KW-5139, but not PGF2 alpha, shortens the reappearance time of the phase III activity in the stomach.