Effects of 5-acetylspiro[benzofuran-2(3H),1'-cyclopropan]-3-one, a new anti-ulcer agent, on experimental acute and chronic ulcers

The effects of 5-acetylspiro[benzofuran-2(3H),1'-cyclopropan]-3-one (AG 629), a newly synthesized compound, on various experimentally induced ulcers were investigated. Oral or intraduodenal administration of AG 629 in a dose range of 25-100 mg/kg inhibited water-immersion stress ulcer, exertion ulcer, Shay ulcer, indometacin- and acetylsalicylic acid (ASA)-induced gastric ulcer, and indomethacin-induced small intestinal ulcer in rats, histamine-induced gastric ulcer in guinea pigs, and ASA-induced gastric ulcer in dogs, though it was not effective against cysteamine-induced duodenal ulcer in rats. AG 629 in doses of 6.3-25 mg/kg p.o. twice a day significantly promoted the healing of acetic acid- or thermal-cortisone-induced gastric ulcers and acetic acid-induced duodenal ulcers in rats. AG 629 (25-100 mg/kg i.d.) inhibited the secretion of gastric acid and pepsin in pylorus-ligated rats and the acid secretion stimulated by distension of the rat stomach with air, whereas this compound did not affect acid secretion stimulated by histamine, pentagastrin, carbachol or 2-deoxy-D-glucose. This study shows that AG 629 has both prophylactic and curative effects on various ulcers. The anti-ulcer effect of this agent seems to be mediated primarily by increasing mucosal resistance and secondarily by an antisecretory activity.     

Effects of a new histamine H2-receptor antagonist, ranitidine, on experimental acute gastric and duodenal ulcers (author's transl)

Ranitidine at 100 to 200 mg/kg (i.d. or p.o.) potently inhibited the development of Shay ulcers, indomethacin- or phenylbutazone-induced gastric ulcers and histamine-carbachol-induced duodenal ulcers in rats. Ranitidine at 100 mg/kg (p.o.) also inhibited the development of water-immersion stress-induced gastric ulcers in rats, histamine-induced gastric and duodenal ulcers in guinea pigs, even though the inhibition rate remained within 70%. At that time, the gastric acid output in guinea pigs was reduced with some doses of the drug. Cimetidine at 100 to 200 mg/kg (p.o.) also inhibited the development of indomethacin-, phenylbutazone-, and water-immersion stress-induced gastric ulcers in rats and histamine-induced gastric and duodenal ulcers in guinea pigs. Shay ulcers and histamine-carbachol-induced duodenal ulcers in rats were not affected by cimetidine. Both ranitidine and cimetidine inhibited the gastric acid output in pylorus-ligated rats (7 hr); the maximal inhibition being 79.6% and 50.7% respectively. The mechanism by which ranitidine inhibits various experimental ulcers might be mainly the inhibition of gastric secretion. Gefarnate at 300 mg/kg (p.o.) significantly inhibited phenylbutazone-induced gastric ulcers in rats but had no effect on other ulcer models.     

Gastric antisecretory and anti-ulcer effect of ME3407, a new benzimidazole derivative, in rats

The effects of a new benzimidazole derivative, ME3407 (n-butyl-2-(thiazolo-[5,4-b]pyrid-2-yl) sulfinylacetate, CAS 133903-90-9), on gastric acid secretion and gastric and duodenal ulcers in rats were examined. ME3407, given orally, inhibited dose-dependently (0.3-30 mg/kg) the incidence of gastric lesions such as Shay ulcers, and water-immersion stress-, acetylsalicylic acid (ASA)- and histamine-induced erosions. In addition, ME3407 showed marked therapeutic effect on HCl- and ASA-induced lesions. In the lumen-perfused rats, oral administration of ME3407 inhibited dose-dependently (1-100 mg/kg) gastric acid secretion induced by histamine and tetragastrin with ED50 values of 3.02 and 3.37 mg/kg, respectively. Oral administration of ME3407 at a dose of 30 mg/kg also inhibited the elevation of serum gastrin level. The development of duodenal ulcers caused by mepirizole and systeamine was also potently inhibited by ME3407 at an oral dose of 0.1-30 mg/kg. However, when given at 30 mg/kg intraduodenally, subcutaneously or intravenously, ME3407 did not inhibit these acutely induced gastric elosion and acid output. ME3407 was not detected in the serum upon oral administration. These results indicated that ME3407 was active only by oral administration, and exerts direct action on the ulcers and acid secretion from the gastric membrane.     

Effects of the novel anti-ulcer agent 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine on experimental ulcers and gastric secretion in rats

The effects of 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285) on various experimentally induced ulcers and gastric acid secretion were investigated in rats. HWA 285 (10-50 mg/kg, p.o.) inhibited restraint and water-immersion-induced stress, ulcers, indometacin- and absolute ethanol-induced gastric ulcers and mepirizole-induced duodenal ulcers in rats in a dose-dependent manner. HWA 285 (10-25 mg/kg i.d.) had inhibitory effects on acetylsalicylic acid-induced ulcers. The healing of acetic acid-induced chronic ulcers was significantly accelerated by HWA 285 (25 mg/kg p.o.) when it was given twice daily for 7 consecutive days. When given orally (twice a day, 11 doses in total) before the induction of gastric ulcers by stress, cimetidine at 100 mg/kg aggravated the ulcers, whereas, HWA 285 at 25 mg/kg had not such an effect. In conscious pylorus-ligated rats, HWA 285 (10-100 mg/kg i.p.) showed a dose-dependent inhibition on basal and desglugastrin- and 2-deoxy-D-glucose (2-DG)-stimulated gastric acid secretion. In stomach-lumen perfused rats, HWA 285 (30 mg/kg i.v.) inhibited 2-DG-stimulated gastric acid secretion but not carbachol-stimulated gastric acid secretion. These results suggest that the anti-ulcer effects of HWA 285 are produced by cytoprotective and central anti-secretory activity without peripheral anti-cholinergic properties. Whether the central anti-secretory effects of HWA 285 play thereby the key role, have to be clarified in further investigation.     

Effects of the new anti-ulcer agent KB-5492 on experimental gastric mucosal lesions and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine.

Effects of KB-5492, a new anti-ulcer agent, on various experimental gastric mucosal lesions and mucosal defensive factors in rats were compared with those of teprenone and cimetidine. KB-5492 administered orally at 12.5-200 mg/kg inhibited water-immersion stress- and indomethacin-induced gastric mucosal lesions in a dose-dependent manner with ED50 values of 46 and 27 mg/kg, respectively, indicating that KB-5492 was more potent than teprenone but less potent than cimetidine. KB-5492, administered orally at 12.5-100 mg/kg, also inhibited ethanol-induced gastric mucosal lesions in a dose-dependent manner with an ED50 of 23 mg/kg, so KB-5492 was 3 times more potent than teprenone, whereas cimetidine produced no obvious inhibition. In addition, KB-5492, administered orally at 25 and 50 mg/kg twice daily for 10 consecutive days, significantly accelerated the healing of acetic acid-induced gastric ulcers more potently than teprenone and cimetidine. KB-5492 at anti-ulcer doses significantly increased gastric mucosal blood flow in normal anesthetized rats and inhibited the reduction of gastric mucosal hexosamine content induced by aspirin, but did not affect gastric acid secretion in pylorus-ligated rats. These results indicate that KB-5492 has potent and broad anti-ulcer properties, which are probably exerted by its enhancement of gastric mucosal defensive factors through increasing gastric mucosal blood flow and/or retaining gastric mucus, and not by its inhibition of gastric acid secretion.     

Fluoxetine and sertraline stimulate gastric acid secretion via a vagal pathway in anaesthetised rats.

The effect of the selective serotonin reuptake inhibitors, fluoxetine and sertraline on basal, secretagogues (histamine or bethanechol)- and distention-stimulated gastric acid secretion was investigated in the urethane-anaesthetised acute gastric fistula rat. Gastric acid secretion was measured by flushing of the gastric contents with saline every 15 min. Fluoxetine (10 or 20 mg kg(-1), i.p.) produced a dose-dependent increase in basal gastric acid secretion. These stimulatory effects were abolished by vagotomy. Intraperitoneally administered sertraline also stimulated gastric acid secretion. The stimulatory effect of lower doses (5 mg kg(-1)) of sertraline was similar to that of the higher (30 mg kg(-1)) doses. The gastric secretory response to i.p. sertraline was long lasting (greater than 60 min), and blocked by vagotomy. Intraperitoneally administered fluoxetine (10 or 20 mg kg(-1)) or sertraline (5 mg kg(-1)) also increased gastric secretion induced by histamine, bethanechol or distention. The fluoxetine or sertraline stimulatory effects of histamine-induced acid secretion were abolished by vagotomy. Data indicate a stimulatory effect for fluoxetine and sertraline mediated by vagal nerve on gastric acid secretion in urethane-anaesthetised rats.     

Effects of MCI-727, a new antiulcer agent, on various gastric and duodenal lesions in experimental animals

Effects of a new antiulcer drug, MCI-727, on gastric and duodenal lesions, gastric secretion and gastric motility were studied in comparison with cimetidine and teprenone. MCI-727 dose-dependently (3-100 mg/kg, p.o. or i.d.) inhibited the development of acute gastric or duodenal lesions such as pyrolus ligation-, water-immersion stress-, indomethacin-, HCl-, HCl-ethanol-induced gastric lesions and cysteamine-induced duodenal lesions in rats and histamine-induced duodenal lesions in guinea pigs. These antiulcer effects exceeded those of cimetidine or teprenone. Repeated administration of MCI-727 (0.3-3 mg/kg/day, p.o., for 10 days) significantly promoted the spontaneous healing of acetic acid-induced chronic gastric ulcers. Concerning gastric acid secretion, MCI-727 selectively inhibited tetragastrin-stimulated acid secretion without effecting basal acid secretion and acid secretion by other stimuli. Cimetidine and teprenone inhibited acid secretion in several cases. MCI-727 and teprenone had inhibitory effects on gastric motility, although cimetidine had no effect. These results suggest that MCI-727 has a wide spectrum of antiulcer activity, and its mode of antiulcer action is different from that of cimetidine or teprenone.     

Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric secretion and experimental ulcers in rats

Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric secretion and experimental ulcers were investigated in rats. Oral administration of TA-2711 at doses of 25 to 100 mg/kg immediately after pyloric ligation markedly reduced pepsin activity and slightly lowered acid concentration without affecting the volume of gastric juice. Addition of TA-2711 (0.25-16 mg/ml) directly to gastric juice also reduced pepsin activity in vitro. Oral TA-2711 dose-relatedly inhibited the formation of pylorus-ligated ulcers (50-200 mg/kg), aspirin-induced gastric erosions (25-100 mg/kg) and cysteamine-induced duodenal ulcers (100-800 mg/kg). In addition, this drug prevented both the formation of gastric lesions (6.3-100 mg/kg, p.o.) and the fall in gastric potential difference (100 mg/kg, p.o.) induced by ethanol. The preventive effect against ethanol-induced lesions was suppressed by pretreatment with indomethacin (10 mg/kg, s.c.). Intravenous dosing of TA-2711 (10-100 mg/kg) never produced such effects on ethanol-induced lesions and pepsin activity as observed by oral administration. These results indicate that TA-2711 exerts its anti-ulcer effect by a local action, and it is suggested that both reduction of pepsin activity and a mucosal prostaglandin-mediated process are involved in the anti-ulcer action of TA-2711.     

Anti-ulcer effect of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl) phenyl] propionic acid hydrochloride (TEI-5103)

The anti-ulcer effects of the newly synthesized compound 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)-phenyl]propionic acid hydrochloride (TEI-5103) on experimentally induced ulcers in rats were studied. TEI-5103 at doses of 25 to 400 mg/kg p.o. prevented formation of ulcers induced by serotonin, indomethacin, acetylsalicylic acid or stress (acute ulcer models), its effect being greater against gastric ulcers induced by serotonin. On acetic acid ulcer (chronic ulcer model), TEI-5103 at a daily dose of 200 mg/kg p.o. accelerated the healing of ulcers. TEI-5103 at doses of 100 to 400 mg/kg i.d. did not inhibit gastric acid secretion in pylorus-ligated rats. It markedly increased gastric blood flow in anesthetized rats (at 10-20 mg/kg i.v., measured by the aminopyrine clearance method), and also increased gastric blood flow in anesthetized dogs (at 2.5-10 mg/kg i.v., measured by the cross thermocouple method). These results indicate that TEI-5103 is effective as an anti-ulcer agent increasing gastric mucosal blood flow and possibly promoting the healing process of peptic ulcers.     

The long-lasting effect of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion in dogs.

We have used Heidenhain-pouch dogs to investigate the effects of (+/-)-5-methoxy-2-{[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulph inyl}-1H-imidazo[4,5-b]pyridine (TU-199), an imidazopyridine derivative, on gastric acid secretion stimulated by histamine, carbachol and tetragastrin. We have also investigated the duration of the antisecretory effect of TU-199 using a measurement of intragastric pH for 24 h in gastric fistula dogs whose gastric acid secretion was stimulated by histamine. Single oral administration of TU-199 (0.1, 0.2 and 0.4mgkg(-1)) dose-dependently suppressed gastric acid secretion stimulated by histamine infusion. Oral treatment with TU-199 (0.2, 0.4 and 0.8 mg kg(-1)) also dose-dependently inhibited acid secretion induced by carbachol and tetragastrin. The inhibitory effect of TU-199 on stimulated gastric acid secretion was more potent than that of omeprazole, a well-known H+,K(+)-ATPase inhibitor in dogs. Repeated oral treatment with TU-199 at a dose of 0.2 mg kg(-1) once a day for seven days markedly suppressed histamine-stimulated gastric acid secretion in dogs. This inhibitory effect of TU-199 reached a maximum level after three or four doses and was more pronounced than that of omeprazole or lansoprazole. In gastric fistula dogs, the duration of intragastric pH-elevation by administration of TU-199 (0.3 mg kg(-1)) was much longer than that of omeprazole (0.6mgkg(-1)) or lansoprazole (0.9mgkg(-1)). The IC50 values (doses resulting in 50% inhibition) of TU-199, omeprazole and lansoprazole with regard to H+,K(+)-ATPase activity in dog gastric mucosal microsomes were 8.6, 8.8 and 9.9 microM, respectively. These results indicate that TU-199 inhibits gastric acid secretion via suppression of a H+,K(+)-ATPase activity. Our findings also suggest that TU-199 might have potent and long-lasting effects on gastric acid secretion.     

Effects of IT-066, a new histamine H2-receptor antagonist, on gastric acid secretion and experimental gastric ulcers in rats and dogs

We examined the effects of a new histamine H2-receptor antagonist, 3-amino-4-(4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2- butenylamino)-3- cyclobutene-1,2-dione hydrochloride (IT-066), on gastric acid secretion and the healing process of experimental ulcers in rats and dogs. Famotidine, a well-established H2-receptor antagonist, was used as the reference drug. Male Donryu rats (240-260 g) and Beagle dogs of both sexes (8-10 kg), having Heidenhain pouches, were used. IT-066 dose-dependently inhibited the basal gastric acid secretion of rats, and this inhibition significantly persisted for 12 hr. In addition, the agent significantly inhibited histamine-stimulated acid secretion in both normal rats and rats with acetic acid ulcers. IT-066, given p.o. twice daily for 2 and 3 weeks after ulceration, significantly accelerated both spontaneous and delayed healing (with indomethacin) of acetic acid-induced gastric ulcers in rats. The effects of IT-066 on acid secretion and ulcer healing were almost the same or slightly more potent than those observed with famotidine. IT-066, when given i.v. or p.o., dose-dependently inhibited the gastric acid secretion stimulated by histamine, pentagastrin, or carbachol in dogs. The antisecretory effects of the agent on histamine-stimulated acid secretion significantly persisted for more than 6 hr. These results indicate that IT-066 appears to be a promising antisecretory and anti-ulcer agent.     

Effects of 2-benzyloxycarbonylphenyl trans-4-guanidinomethylcyclohexanecarboxylate hydrochloride monohydrate (TKG01) and its clathrate compound with beta-cyclodextrin (TA903) on experimental gastric ulcers and gastric secretion in rats

Effects of TKG01 on gastric ulcers and gastric secretion in rats were investigated in comparison with those of TA903, which is the equimolar clathrate compound of TKG01 anhydride with beta-cyclodextrin. The doses were adjusted on a molecular weight basis to include the same amount of TKG01 anhydride. Water-immersion stress ulcers were dose-dependently (100, 300 mg/kg) inhibited by TA903 given orally, but only significantly inhibited by TKG01 (300 mg/kg). TA903, given orally, even in low doses (30, 100 mg/kg) potently inhibited HCl-ethanol ulcers, whereas TKG01 did not inhibit these ulcers. Both TA903 and TKG01, given orally (100, 300 mg/kg), showed similar inhibition of indomethacin ulcers. TA903, given intraduodenally (100, 300 mg/kg), dose-dependently inhibited gastric secretion (volume, acid output and pepsin output) in pylorus-ligated rats, but TKG01 only inhibited pepsin output (100, 300 mg/kg). These results showed that TA903 had a broader spectrum of anti-ulcer effects than TKG01 and the mechanism of TA903 could involve both its cytoprotective activity and its anti-secretory effect.     

Peripheral GABAB agonists stimulate gastric acid secretion in mice

1 We characterized the effects of intravenous GABA and preferential GABAA (muscimol), GABAB (R-baclofen and SKF-97541) and GABAC agonists (imidazole-4-acetic acid) on gastric acid secretion in urethane-anesthetized mice implanted with a gastric cannula, and determined the role of vagal cholinergic mechanisms, and gastrin and somatostatin by using peptide immunoneutralization, the SSTR2 antagonist, PRL-2903, and SSTR2 knockout mice. 2 The selective GABA(B) agonists R-baclofen (0.1-3 mg kg(-1), i.v.) and SKF-97541 (0.01-0.3 mg kg(-1), i.v.) induced a dose-related stimulation of gastric acid secretion. SKF-97541 was about 10 times more potent than R-baclofen stimulating gastric acid secretion. Neither GABA (0.1-100 mg kg(-1), i.v.) nor muscimol (0.1-3 mg kg(-1)) nor imidazole-4-acetic acid (0.1-10 mg kg(-1)) affected basal gastric acid secretion. 3 Stimulatory effects of SKF-97541 (0.1 mg kg(-1), i.v.) were blocked by the selective GABAB antagonist, 2-hydroxysaclofen, cholinergic blockade with atropine, subdiaphragmatic vagotomy or gastrin immunoneutralization. 4 Somatostatin immunoneutralization or SSTR2 blockade with PRL-2903 enhanced the secretory response to SKF-97541 (0.1 mg kg(-1), i.v.) by 78 and 105%, respectively. 5 In SSTR2 knockout mice, SKF-97541 (0.1 mg kg(-1), i.v.) increased basal gastric acid secretion by 48%. Neither GABA nor muscimol nor imidazole-4-acetic acid modified basal gastric acid secretion in SSTR2 knockout mice. 6 These results indicate that, in mice, stimulation of GABAB receptors increases gastric acid secretion through vagal- and gastrin-dependent mechanisms. Somatostatin implication might be secondary to the release of gastrin and the increase in gastric luminal acidity.     

吡咯-2-甲醛缩N4-(4-甲氧基苯基)氨基脲抗实验性大鼠溃疡作用

化合物Ⅰ具有与呋喃唑酮相似的抗实验性大鼠溃疡活性,但小鼠口服急性毒性较后者小。化合物Ⅰ在剂量为40～100 mg/kg时对五种大鼠溃疡模型(消炎痛型、幽门结扎型、慢性醋酸型、和无水乙醇引起的大鼠溃疡模型)均有较好保护作用,但对水拘急性应激型溃疡无效。对胃酸分泌无明显影响,对胃蛋白酶分泌有轻度抑制作用;具有“细胞保护”样作用,对HCl和无水乙醇引起的大鼠溃疡显示出较好的保护作用;增加幽门结扎大鼠胃液中氨基己糖的含量,降低DNA含量。     

Effects of trimoprostil on healing and recurrence of acetic acid-induced gastric ulcer in rats

Chronic gastric ulcers were produced by injection of 20% acetic acid (0.05 ml) into the submucosal layer of the rat stomach in order to determine the effects of the prostanoid trimoprostil on the healing and recurrence of ulcers. Local injection of acetic acid solution produced large demarcated ulcers in all animals on day 5, which rapidly decreased to reach low levels on days 40-80 and then became exacerbated on day 100. The exacerbation of the ulcer is probably recurrence. Trimoprostil was administered ad libitum in drinking water containing 0.1, 0.3 and 1.0 microgram/ml (average dose 12.4, 37 and 124 micrograms/kg/day) for a period of 14 days (day 1-15) to assess its effect on healing and for a period of 40 days (day 60-100) to assess its ability to prevent recurrence. The higher two doses of trimoprostil accelerated the spontaneous healing of the ulcers. Furthermore, trimoprostil, at both doses, prevented the observed recurrence of this type of ulcer. Trimoprostil dose-dependently (30-300 micrograms/kg, p.o.) inhibited gastric secretion in pylorus-ligated rats. Cimetidine at the antisecretory dose (1 mg/ml, 132 mg/kg/day) failed to affect the healing process of gastric ulcers, but tended to prevent the recurrence of gastric ulcers. Our present study suggests that trimoprostil is a promising antiulcer drug for the treatment of chronic gastric ulcer.     

四种多糖抗溃疡作用的研究

糊精、人参果胶、肝素和硫酸软骨素A对四种大鼠实验性胃溃疡(消炎痛型、应激型、幽门结扎型及醋酸型)均有不同程度的抑制作用,前两种植物多糖抗溃疡作用比后两种酸性粘多糖强。其中以糊精的抗溃疡作用最显著。多糖的抗溃疡作用可能与其降低胃酸和抑制胃蛋白酶活性有关。     

Inhibition of gastric H+, K(+)-ATPase and acid secretion by ellagic acid.

The effects of ellagic acid on gastric H+, K(+)-ATPase, acid secretion, and the occurrence of gastric ulcers were studied. Ellagic acid inhibited hog gastric H+, K(+)-ATPase activity with a 50% inhibition at 2.1 x 10(-6)M; kinetic studies showed that the inhibition of H+, K(+)-ATPase by ellagic acid is competitive with respect to ATP and is noncompetitive with respect to K+. The effect on gastric ulcers was investigated by using a stress ulcer model. Intraperitoneal administration of ellagic acid at above 5 mg/kg markedly reduced the occurrence of gastric lesion. Ellagic acid significantly reduced acid secretion at the same doses. These results suggest that ellagic acid has a marked inhibitory effect on acid secretion and the occurrence of stress-induced gastric lesions, and these effects may be attributed to the inhibition of H+, K(+)-ATPase activity.     

Effect of metiamide, a histamine H2 - receptor antagonist, on the development of gastric stress ulcers and acid secretion.

In normal and stressed rats with chronic gastric fistula small doses of metiamide (0.001-0.01 muM/kg) increased and doses of over 20 muM/kg decreased gastric acid secretion. In both these dose ranges of dosage metiamide suppressed the development of stress ulcers, most markedly in doses of 0.005 and 100 muM/kg. Intermediate doses had no such action. Only the anti-ulcer action of large doses of metiamide ran parallel to a reduction in acid secretion. Small doses of metiamide increased gastric secretion, but like larger doses, had a weak adrenergic action.     

Effects of FRG-8813, a new-type histamine H2-receptor antagonist, on the healing of gastric and duodenal ulcer in rats and spontaneously ulcerative mice]

We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given orally twice a day for 7 days, accelerated the healing of gastric or duodenal ulcer induced by acetic acid injection or application at the non-antisecretory doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813 were more potent than those of famotidine or cimetidine. In W/WV mice, several ulcers spontaneously developed on gastric mucosa during the 8 weeks after the birth. The ulcers were aggravated by several unknown factors after the ulcer generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we suggest that FRG-8813 is able to accelerate the healing of ulcers by antisecretory plus increasing actions on the integrity of the gastric mucosal defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the treatment of gastric or duodenal ulcers in humans.