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.     

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 proton pump inhibitor, AG-1749 (lansoprazole), on reflux esophagitis and experimental ulcers in rats

The effects of (+/-)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy-2- pyridyl]methyl]sulfinyl]-1H-benzimidazole (lansoprazole, AG-1749) and famotidine on various experimental ulcers in rats were compared. AG-1749 inhibited reflux esophagitis; gastric lesions induced by water-immersion stress, aspirin or ethanol; and duodenal ulcers induced by cysteamine or mepirizole in a dose-dependent manner: the ID50 values were 0.7, 2.4, 0.7, 8.5, 1.1 and 0.3 mg/kg, p.o. or i.d., respectively. Famotidine inhibited reflux esophagitis with an ID50 value of 12.9 mg/kg, but did not cause 50% inhibition of ethanol-induced gastric lesions even at 100 mg/kg, although it showed almost the same or a little stronger potency on other experimental ulcers: ID50 values were 0.3-1.4 mg/kg. Significant aggravation of ethanol- or water-immersion stress-induced lesions was observed in rats given famotidine at 30 mg/kg twice daily for 4 days, but not in rats given AG-1749 at 10 mg/kg twice daily. Administration of AG-1749 for 14 consecutive days markedly accelerated the healing of acetic acid-induced gastric and duodenal ulcers, and the healing effect was significant at 10 and 30 mg/kg/day, p.o. Famotidine also accelerated the healing of ulcers, but its potency was less than that of AG-1749. The results of this study indicate that although AG-1749 is slightly less potent than famotidine in inhibiting acutely induced gastroduodenal lesions, this agent is superior to famotidine in promoting the healing of ulcers and in inhibiting reflux esophagitis and ethanol-induced gastric lesions.     

Studies on the healing promoting action of Z-103 in chronic gastric ulcer models of rats]

We studied the healing promoting action of Z-103 on the chronic gastric ulcer induced by acetic acid (AAU) or Fe-ascorbic acid (FAU) in rats. The area of the gastric ulcers, hydroxyproline (Hyp) and DNA contents in the ulcer region were measured as an index of ulcer healing. The area of gastric ulcers was the largest on day 4 and thereafter gradually decreased, but the ulcers still remained at the 14th day. Hyp contents in the ulcer region decreased until the 7th day in both models, and then this level increased. Significant decrease in DNA contents in the ulcer region was observed on the 7th day only in FAU. In AAU and FAU, administration of Z-103 (3 mg/kg/day x 2, p.o.) resulted in a significant decrease in the area of gastric ulcers on the 14th day and a significant increase in Hyp contents in the ulcer region on the 7th day as compared with the control group. Z-103 increased the DNA contents in the ulcer region on the 4th day in AAU and on the 7th day in FAU. These results suggest that tissue destruction surrounding the ulcer region in AAU and FAU models might occur until the 4th or 7th day after operation, and that the acceleration of ulcer healing by Z-103 on these models may be facilitated by the wound healing action of this drug.     

Anti-ulcer effect of tea catechin in rats

Oral administration of tea catechin dose-dependently prevented absolute ethanol-induced (50, 100, 200 mg/kg) or restraint plus water immersion stress-induced acute gastric mucosal injury (300, 400 mg/kg) in rats. When the effect of test compound was evaluated on the 15th day after acetic acid injection to rats, repeated oral administration of tea catechin (25, 50, 100 mg/kg twice daily) dose-dependently accelerated the healing of acetic acid-induced chronic gastric ulcers. Tea catechin (10(-5)-10(-1) g/100 ml) concentration-dependently scavenged superoxide anions in vitro. Tea catechin (100, 200 mg/kg orally) markedly inhibited the increase in thiobarbituric acid-reactive substances in the injured mucosa of rats treated with 50% ethanol. Tea catechin (50, 100 mg/kg twice orally, daily) markedly inhibited the increase in content of thiobarbituric acid-reactive substances in the ulcerated region of acetic acid-induced gastric ulcers on the 7th and 15th days. In addition, at 50, 100 and 200 mg/kg orally, it dose-dependently prevented the decrease in gastric mucosal hexosamine content induced by absolute ethanol, although it failed to inhibit the basal gastric acid secretion. These results suggest that tea catechin may primarily protect gastric mucosa from acute gastric mucosal injury and promote the healing of chronic gastric ulcers by its antioxidant activity and gastric mucus-increasing actions.     

脑室注射催产素对大鼠胃和十二指肠溃疡的作用

INTRODUCTION Central neurons that synthesize oxytocin are locatedin the supraoptic(SON) and paraventricular nuclei(PVN) of the hypothalamus. Magnocellular neurons inboth nuclei project to the posterior pituitary gland,     

Teprenone promotes the healing of acetic acid-induced chronic gastric ulcers in rats by inhibiting neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues.

Teprenone, an anti-ulcer drug, has been reported to promote the healing of acetic acid-induced chronic gastric ulcers in rats by stimulating gastric mucus synthesis and secretion. Recently, it has been implicated that neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues have an inhibitory effect on the healing of acetic acid-induced chronic gastric ulcers in rats. Therefore, we attempted to clarify whether teprenone exerts a healing-promoting effect on acetic acid-induced chronic gastric ulcers through its inhibitory effect on neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. In rats with chronic gastric ulcers made by applying acetic acid to the stomach, gastric ulcer healing started later than 3 days after the acetic acid application. Gastric mucosal myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, and lipid peroxide content were higher in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application. Gastric mucosal non-protein SH content was lower in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application, and gastric mucosal adherent mucus content was lower in the ulcerated region than in the intact region on the 8th and 15th day. Daily oral administration of teprenone (100 mg kg(-1)x 2) for 7 or 14 days, starting on the 8th day after the application of acetic acid to the stomach, enhanced the reduction of the ulcer area with attenuation of all these biochemical changes found in the ulcerated region. The teprenone administration caused a decrease in MPO activity and an increase in adherent mucus content in the gastric mucosa of the intact region. These results suggest that the healing-promoting effect of teprenone on acetic acid-induced chronic gastric ulcers in rats could be due not only to stimulation of gastric mucus secretion but also to inhibition of neutrophil infiltration and enhanced lipid peroxidation in the ulcerated gastric tissue.     

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.     

Healing promoting effect of azuletil sodium (KT1-32) on experimental chronic gastric ulcers and acceleration of healing in SPF environment

We examined the healing promoting effects of azuletil sodium on acetic acid and clamping cortisone-induced gastric ulcer in rats. For the experiments on clamping-cortisone gastric ulcer, we used not only conventional rats in conventional conditions but also specific pathogen free (SPF) rats on SPF environment in order to prevent infection. The following results were obtained. 1) In acetic acid ulcer, azuletil sodium (AZE) (greater than or equal to 90 mg/kg/day, p.o.) significantly decreased ulcer index. As estimated on the basis of stage analysis (Ulcer, Healing, Scar), AZE (greater than or equal to 30 mg/kg/day, p.o.) significantly promoted the healing of ulcers. 2) In clamping cortisone ulcer (conventional), AZE (100 mg/kg/day, p.o.) significantly promoted the regeneration of blood vessels. 3) In clamping cortisone ulcer (SPF), AZE at greater than or equal to 30 mg/kg/day and 100 mg/kg/day significantly increased the healing index and mucosal regeneration index, respectively. 4) In clamping cortisone ulcer (SPF), the infection that was observed in the conventional test was not seen at all and the acceleration of healing was observed. Furthermore, the extent of adhesion was also reduced, and the standard errors of various healing indices were smaller. From these results, it is concluded that AZE accelerated the healing of experimentally-induced gastric ulcers in rats.     

Effects of cimetidine and atropine sulfate on gastric secretion and healing of gastric and duodenal ulcers in rats.

Cimetidine, a new histamine H2-receptor antagonist (50 or 100 mg/kg) and atropine sulfate (15 mg/kg) given intraduodenally, markedly inhibited gastric secretion in pylorus-ligated rats. Cimetidine (100 or 200 mg/kg/day) given for 10 or 12 consecutive days orally in two divided doses, significantly promoted the healing rate of both gastric and duodenal ulcers induced in rats. Atropine (30 mg/kg/day) also significantly accelerated the healing of duodenal ulcers but failed to affect gastric ulcers.     

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.     

Antiulcer activity of cod liver oil in rats

Objective:

Cod liver oil is used widely as a dietary supplement. The present study was carried out to evaluate the effect of cod liver oil (0.5 g/kg, p.o. and 1 g/kg, p.o.) on gastric and duodenal ulcers.

Materials and Methods:

The study was carried out on different gastric ulcer models such as acetic acid induced chronic gastric ulcers, pylorus ligation, indomethacin induced ulcers, stress induced ulcers and ethanol induced ulcers. The duodenal ulcers were induced using cysteamine hydrochloride (HCl). Ranitidine (50 mg/kg p.o.) and misoprostol (100 µg/kg, p.o.) were used as standard drugs.

Results:

Both doses of cod liver oil showed gastric ulcer healing effect in acetic acid induced chronic gastric ulcers, produced gastric antisecretory effect in pylorus-ligated rats and also showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced ulcer. Cod liver oil also produced a significant reduction in the development of stress induced gastric ulcers and cysteamine induced duodenal ulcer. The high dose of cod liver oil (1 g/kg, p.o.) was more effective compared to the low dose (0.5 g/kg, p.o.).

Conclusion:

Cod liver oil increases healing of gastric ulcers and prevents the development of experimentally induced gastric and duodenal ulcers in rats.     

Effects of 3-hydroxymethyl-2-methylimidazo [2, 1-b] benzothiazole (NIK-228) on gastric acid secretion and various experimental peptic ulcers in rats

We examined the antisecretory and antiulcer activities of NIK-228 in rats. Male Wistar rats (200 to 250 g) were used under 24 to 48 hr fasted (without water) conditions. NIK-228 and famotidine were administered orally 1 hr before pylorus ligation, stress or each ulceration inducer. Both NIK-228 (10 to 100 mg/kg) and famotidine (0.3 to 3 mg/kg) dose-dependently inhibited gastric secretion in pylorus ligated rats. Water-immersion stress-, indomethacin- or pylorus ligation (Shay)-induced gastric ulcers were dose-dependently inhibited by NIK-228 (10 to 100 mg/kg), but only water-immersion stress and indomethacin induced ulcers were dose-dependently inhibited by famotidine (0.03 to 3 mg/kg). Ethanol- and 0.6 N HCl-induced gastric lesions were remarkably inhibited by NIK-228 (ED50 = 2.7 and 5.6 mg/kg), but tended to be inhibited also by famotidine (0.3 to 3 mg/kg). Cysteamine-induced duodenal ulcer was inhibited significantly by NIK-228 (30, 100 mg/kg) or famotidine (3 mg/kg). NIK-228 may produce its antiulcer effects via antisecretory and cytoprotective effects. These results suggest that NIK-228 has antisecretory and antiulcer activities.     

Effect of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) on healing and hydrocortisone-induced relapse of acetic acid ulcers in rats with limited food-intake-time

In the healing test of acetic acid ulcers in rats with limited food-intake-time, Z-103 given, p.o., at doses of 3 and 10 mg/kg, twice a day, for 14 consecutive days from the day after acetic acid injection not only reduced the size and depth of the ulcers, but also promoted the regeneration of the defective mucosa. In the hydrocortisone-induced relapse test of acetic acid ulcers in rats with limited food-intake-time, Z-103 given, p.o., twice a day, at doses of 3 and 10 mg/kg for 20 consecutive days from the 40th day after the acid injection strongly prevented the exfoliation of the regenerated mucosa. Cimetidine (100 mg/kg x 2/day, p.o.), like Z-103, showed a marked relapse-preventive action in addition to the healing-promoting action. However, it was more effective on the healing. Gefarnate (300 mg/kg x 2/day, p.o.) markedly reduced the size and depth of the ulcers and strongly prevented the steroid-induced relapse, but showed no apparent effect on the regeneration of the defective mucosa. These results suggest that Z-103 may be a new therapeutic agent sharing both healing-promoting and relapse-preventive actions on gastric ulcers.     

Effects of pantoprazole on ulcer healing delay associated with NSAID treatment

Nonsteroidal anti-inflammatory drugs delay gastric ulcer healing, and the ability of proton pump inhibitors to counteract this detrimental effect is debated. This study evaluates the effects of pantoprazole on experimental gastric ulcer healing in the presence of indomethacin. Rats with acetic-acid-induced gastric ulcers were orally treated for 3 or 7 days with pantoprazole (15 mumol/kg/day) or famotidine (20 mumol/kg/day), alone or in combination with indomethacin (3 mumol/kg/day). Ulcerated tissues were processed to assess ulcer area, malondialdehyde, proliferating cell nuclear antigen (PCNA) and cleaved caspase-3. Experiments on pylorus-ligated rats indicated that pantoprazole and famotidine were employed at equivalent inhibitory doses on gastric acid secretion (-67.9% and -64.5%, respectively). Indomethacin delayed ulcer healing both at days 3 and 7 (+22 and +35 mm(2) vs control ulcer, respectively). At day 3, pantoprazole was more effective than famotidine in promoting ulcer healing in indomethacin-treated animals (-53.6 and -31.6 mm(2) vs indomethacin, respectively). Malondialdehyde levels and caspase-3 activation in ulcers were increased by indomethacin (+79% and +3.7 folds vs control ulcer, respectively), and these effects were counteracted by pantoprazole (-77.9% and -3.5 folds vs indomethacin, respectively), but not famotidine. Increments of ulcer PCNA expression (+2.5 folds vs normal) were enhanced further by pantoprazole or famotidine, alone or in combination with indomethacin (+8.6 and +10.3 folds vs normal, respectively). Similar results were obtained after 7-day treatments of ulcerated animals with test drugs. It is concluded that, along with acid suppression, pantoprazole exerts acid-independent effects on ulcer healing, which can be ascribed to a decrease in tissue oxidation and apoptosis.     

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.     

胃散对胃溃疡模型大鼠胃黏膜保护作用的研究

目的 研究胃散对胃溃疡大鼠胃黏膜的保护作用。方法 采用乙酸烧灼型胃溃疡模型、幽门结扎型胃溃疡模型、乙醇损伤型胃溃疡模型,检测溃疡指数、胃酸总酸度、胃酸分泌速度和胃蛋白酶活性,综合考察胃散对胃溃疡模型大鼠胃黏膜的保护作用。结果 胃散在1、0.5、0.25 g/kg剂量下,对乙酸烧灼型胃溃疡有非常显著的促愈合作用;对幽门结扎型胃溃疡的形成有显著的抑制作用;对乙醇损伤的胃黏膜也有显著的保护作用;对胃液总酸度、胃酸分泌速度和胃蛋白酶活性有明显抑制作用,显著增加胃液分泌量。结论 胃散具有增加胃液分泌、抑制胃酸分泌、抑制胃蛋白酶活性、保护胃黏膜和防止胃溃疡的作用。     

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.     

Effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various gastric lesions induced in rats

We studied the effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various acute and chronic gastric lesions produced in rats. Arbaprostil significantly inhibited gastric secretion in 4 hr-pylorus-ligated preparations when given intraduodenally in a dose of 30 or 100 micrograms/kg. The agent, however, significantly stimulated gastric secretion of rats with either a ligated or intact pylorus when given orally in doses of 3-100 micrograms/kg. Orally administered arbaprostil dose-dependently prevented the development of HCI-ethanol-, histamine-, water-immersion stress-, or indomethacin-induced gastric erosions. Intraduodenally administered arbaprostil also dose-dependently prevented the development of aspirin-induced gastric erosions in pylorus-ligated rats. Arbaprostil, given orally in doses of 1-100 micrograms/kg twice daily for 2 weeks, had little or no effect on the healing of acetic acid-induced gastric ulcers. However, oral administration of the agent in a dose of 3 or 10 micrograms/kg twice daily for 4 weeks significantly accelerated the healing of acetic acid-induced gastric ulcers. The increase in doses up to 100 micrograms/kg twice daily for 4 weeks had no effect on ulcer healing. These results indicate that arbaprostil, at either antisecretory or even acid stimulating doses, is effective in preventing the development of acute gastric erosions and in accelerating the healing of chronic gastric ulcers.     

High quality of ulcer healing in rats by lafutidine, a new-type histamine H2-receptor antagonist: involvement of capsaicin-sensitive sensory neurons

This study was conducted to determine whether the low recurrence rate of ulcers after treatment with lafutidine, an antiulcer drug possessing both an antisecretory and gastroprotective activities, was mediated by capsaicin-sensitive sensory neurons (CSSN). Chronic gastric ulcers in rats were induced by serosa-searing. The ulcer healing and recurrence were evaluated by endoscopy. Drugs were orally administered. Desensitization of CSSN was induced by pretreatment with capsaicin. Lafutidine (30 mg/kg) accelerated the ulcer healing significantly, and the recurrence rate was much lower than that for the vehicular control. In CSSN-desensitized rats, lafutidine also accelerated the ulcer healing significantly, but the low recurrence rate shown in normal rats was counteracted. The recurrence rate of the combination of famotidine (30 mg/kg) and teprenone (100 mg/kg) was lower than that of famotidine alone. In conclusion, the low recurrence rate of ulcers after lafutidine treatment in rats seems to depend on the gastroprotective mechanisms involving CSSN.