[Studies on anti-ulcer effects of a new compound, zinc L-carnosine (Z-103)].
We investigated the anti-ulcer effects of zinc L-carnosine (Z-103) using several acute experimental models of gastric and duodenal lesions in rats. Effects of Z-103 on various gastric functions, e.g., antacid (in vitro), anti-pepsin (in vitro), gastric secretion, mucosal potential difference (PD) and mucus contents were also examined. Z-103 given orally prevented development of gastric lesions induced by water immersion stress, histamine, HCl-aspirin, HCl-ethanol and also duodenal ulcers induced by mepirizole in a dose-dependent manner. In vitro, Z-103 had a greater antacid effect than sodium bicarbonate; and moreover, the potency of its anti-peptic action (IC50 = 8.7 mM) was higher than those of several other drugs (sodium bicarbonate, sucrose sulfate and aceglutamide aluminum). Intragastric treatment of Z-103 (100 mg/kg alone tended to increase PD, and it also significantly inhibited the decrease in PD induced by aspirin. In addition, pretreatment with Z-103 at 10 and 30 mg/kg (p.o.) significantly prevented the decrease in mucus contents in the gastric mucosa and also mucosal lesions by oral administration of ethanol. On the other hand, Z-103 was not so effective on both basal (pylorus-ligation preparation) and histamine-stimulated gastric secretion (Heidenhain pouch preparation). These results suggest that Z-103 is useful for the treatment of gastric and duodenal ulcers in humans.
Seiki
M
M
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Ueki
S
S
Tanaka
Y
Y
Soeda
M
M
Hori
Y
Y
Aita
H
H
Yoneta
T
T
Morita
H
H
Tagashira
E
E
Okabe
S
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin; D002336:Carnosine / Q000031:analogs & derivatives*; D004285:Dogs; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D004840:Epirizole; D000431:Ethanol; D005744:Gastric Acid / Q000378:metabolism; D006632:Histamine; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010434:Pepsin A / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D013312:Stress, Physiological; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D004840:Epirizole; D000431:Ethanol; D006632:Histamine; D002336:Carnosine; D010434:Pepsin A; D001241:Aspirin