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1.
Prostaglandin E2 and carbenoxolone, putative cytoprotective agents, were tested in cysteamine, reserpine and stress ulcers in rats. In cysteamine-induced duodenal ulcer, PGE2 was inactive at 0.1 and 0.5 mg/kg p.o.; carbenoxolone at 100 mg/kg p.o. decreased the incidence but not the severity of the ulcer. PGE2 at 5.0 mg/kg p.o. and carbenoxolone at 300 mg/kg p.o. showed moderate effects, but the dosage also inhibited cysteamine-stimulated acid secretion. PGE2 (0.1 and 0.3 mg/kg p.o.) was inactive and carbenoxolone (100 and 300 mg/kg p.o.) further aggravated the gastric ulceration caused by reserpine or cold-restraint stress. In contrast, atropine (3 and 10 mg/kg p.o.) and cimetidine (30, 100 and 300 mg/kg p.o.) were active in all three ulcer models. But the results with cimetidine in stress ulcer were somewhat variable. 2-methyl-8-(phenylmethoxy) imidazo [1,2-a] pyridine-3-acetonitrile (Sch 28 080), a novel structure with both cytoprotective and antisecretory activity, was highly efficacious in cysteamine, reserpine and stress ulcers (1-30 mg/kg p.o.), which was presumably adequately accounted for by its potent antisecretory activity. It is concluded that cysteamine, reserpine and stress ulcers may not be appropriate models for testing the potential antiulcer effect of primarily cytoprotective compounds. 相似文献
2.
1. Propyl-methylenedioxyindene (pr-MDI) is an intracellularly acting calcium antagonist which protects against cold/restraint-induced stress ulcers in rats. The doses of pr-MDI which produce antiulcer activity (10-30 mg/kg i.p.) are significantly lower than those which exhibit cardiovascular effects. 2. Two potential mechanisms for the antiulcer action of pr-MDI were investigated in this study: the effects on hydrochloric acid secretion and on gastric motility (gastric emptying). 3. Bethanechol-induced hydrochloric acid secretion in acutely pylorus-ligated rats was significantly obtunded by pr-MDI (30 mg/kg i.p.), but the effect was significantly weaker than that produced by verapamil (16 mg/kg i.p.) or cimetidine (10 mg/kg i.p.). Since 30 mg/kg pr-MDI produces greater antiulcer activity than the very high dose of 16 mg/kg verapamil, it is unlikely that inhibition of acid secretion plays more than a contributory role in the antiulcer mechanism of action of pr-MDI. 4. pr-MDI (10-30 mg/kg i.p.) produced a dose-dependent slowing of gastric emptying in rats fed a methylcellulose/Phenol Red test meal, and this effect correlated well with the antiulcer action. Verapamil (16 mg/kg i.p.) did not affect gastric emptying. 5. The results indicate that a reduction of gastric motility plays a major role in the mechanism of the antiulcer action of pr-MDI. 相似文献
3.
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. 相似文献
4.
S Yamazaki M Kawamura M Kitsukawa K Ando I Nitta A Tobe S Okabe 《Japanese journal of pharmacology》1991,55(4):415-424
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. 相似文献
5.
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. 相似文献
6.
The antiulcer activity of BAY P 14551 a thiazolylaminobenzimidazole derivative, was evaluated in different experimental ulcer models and its antiulcer activity was compared to that of different reference drugs. The overall activity of the compound was equal to or more potent than that of reference antiulcer drugs, such as pirenzepine, cimetidine and carbenoxolone, but it was not as potent as rioprostil. The ED50 values (expressed as mumol/kg p.o.) were 68 (confidence limits: 51-91) for indomethacin-induced ulcers, 21 (confidence limits: 13-31) for stress-induced ulcers and 1260 mumol/kg p.o. (confidence limits: 412-3800) for ulcers induced by absolute ethanol. The compound had no activity against cysteamine-induced duodenal ulcers and lost its cytoprotective activity in adrenalectomised rats. Since inhibition of gastric acid secretion was seen, if at all, only with the higher doses, the gastro-protective action of BAY P 1455 seemed not to be due to an antisecretory effect, but more likely to a gastroprotective action as hypothesised for prostaglandins. 相似文献
7.
Effects of DQ-2511, a new peripherally acting anti-ulcer agent, on vagally induced gastric acid output and mucosal blood flow (MBF) were investigated in urethane-anesthetized rats with gastric fistula. Intravenous infusion of DQ-2511 (2 or 20 mg/kg/hr, for 30 min) reduced the vagally induced gastric acid output and MBF, and these inhibitory effects were abolished by pretreatment with phentolamine. The DQ-2511-induced inhibition of acid output was abolished with yohimbine, but not with prazosin. These observations suggest that DQ-2511 possesses the properties of an adrenergic alpha-2-adrenoceptor agonist. DQ-2511 presumably acts on adrenergic alpha-2-adrenoceptors located on the parasympathetic neurons in the gastric wall, thereby reducing the vagally-induced gastric acid output. 相似文献
8.
DS-4574 is a peptidoleukotriene antagonist with mast cell stabilizing activity. In the present study, we studied the effects of this compound on gastric secretion and various acute gastric lesions in rats. Intraduodenal administration of DS-4574 at doses of 5 to 10 mg/kg significantly and dose-dependently inhibited gastric acid secretion in pylorus-ligated rats, but a further increase in the dose up to 50 mg/kg did not cause any further inhibition. Shay ulceration in response to pylorus ligation was dose-dependently prevented by DS-4574 (10-25 mg/kg, i.d.). Water-immersion restraint stress- and aspirin-induced gastric ulcers were also significantly prevented in a dose-related manner by oral pretreatment with DS-4574 (10-50 mg/kg). The lower doses of DS-4574 (1-10 mg/kg, p.o.) significantly and dose-dependently protected the gastric mucosa against the necrotizing action of either absolute ethanol or concentrated hydrochloric acid, indicating that this compound possesses a potent gastroprotective activity. These antiulcer and gastric protective effects of DS-4574 were more potent than those of cimetidine used as a reference drug. These findings suggest that DS-4574 is useful for peptic ulcer therapy, as well as for the therapy of various allergic diseases, including asthma. 相似文献
9.
M Kagoshima R Hoshino H Shimada 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1991,98(2):99-111
We have reported the antiulcer activities of a new compound that we named NIK-228 (3-hydroxy-methyl-2-methylimidazo [2, 1-b] benzothiazole). In the present report, we studied the antisecretory effects of NIK-228 on basal and stimulated gastric acid secretion using the Congo red sprayed method. Male Wistar rats (200 to 250 g) were used after 24 hr of fasting (without water). NIK-228, atropine and cimetidine were administered orally or intravenously 1 hr before operation for Congo red spraying. NIK-228 (100 mg/kg, p.o.), atropine (5 mg/kg p.o.) and cimetidine (100 mg/kg, p.o.) all inhibited basal gastric acid secretion. Oral administration of NIK-228 and atropine inhibited gastrin, 2-deoxy-D-glucose (2-DG) and bethanechol-induced acid secretion, but didn't inhibit histamine-induced acid secretion. Cimetidine inhibited all of histamine, gastrin, 2-DG and bethanechol-induced acid secretion. In vagotomized rats, oral and intravenous administration of atropine both inhibited bethanechol-induced acid secretion, but NIK-228 was not inhibited. These results suggested that antisecretory effects of NIK-228 were caused by the central vagal systems. 相似文献
10.
S Okabe H Kunimi H Ohtsuki 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1981,77(4):397-406
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. 相似文献
11.
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. 相似文献
12.
The effects of the dried stem powder of Opuntia ficus-indica var. saboten (OF-s) were investigated on gastric lesion and ulcer models in rats. It showed significant inhibition in HCl ethanol-induced gastric lesion at the doses of 200 and 600 mg/kg p.o. and in HCl.aspirin-induced gastric lesion at 600 mg/kg p.o. OF-s also showed significant inhibition in indomethacin-induced gastric lesion at the doses of 200 and 600 mg/kg, p.o. However, it did not affect both the aspirin-induced and Shay ulcers in rats. It also did not affect gastric juice secretion, acid output and pH. These data indicate that OF-s only possesses pronounced inhibitory action on gastric lesion without antiulcer activity in rats. 相似文献
13.
Gastric antral ulcers produced by the combined administration of indomethacin with 2-deoxy-D-glucose in the rat 总被引:1,自引:0,他引:1
The influence of 2-deoxy-D-glucose (2DG) on indomethacin ulcers was studied in rats. 2DG (200 mg/kg i.v.) produced large round ulcers in the lesser curvature of the antrum and aggravated lesions of the corpus 6 h after treatments in indomethacin (40 mg/kg i.p.)-treated rats. Insulin (5 units/kg i.v.) also produced gastric antral ulcers similarly to 2DG. Antral ulcers were revealed rather clearly 48 h after the administration of indomethacin and 2DG when the corpus lesion index was reduced. 2DG or insulin had only a slight influence on the severity of other experimental gastric ulcers. Peripheral gastric secretagogues, bethanechol (1 mg/kg s.c. X 2) or histamine (10 mg/kg s.c. X 2) did not produce antral ulcers at the gastric secretory dose in the indomethacin-treated rats. High doses of atropine (1.0 and 10 mg/kg s.c.) prevented gastric antral ulcers. The combined administration of indomethacin with 2DG produced gastric antral ulcers similar to human gastric ulcers in rats. The combination of gastric acid secretion, vagus nerve stimulation and some other factors may be involved in gastric antral ulcers produced in rats. 相似文献
14.
M Muramatsu Y Isobe I Arai H Hirose-Kijima C Usuki-Ito H Nagai H Aihara S Otomo 《Arzneimittel-Forschung》1990,40(1):49-54
The effect of 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis- 2-butenylamino]-3-cyclobutene-1,2-dione hydrochloride (IT-066), a new H2-receptor antagonist, on gastric acid secretion and on various experimental ulcers was investigated. IT-066 showed very potent and long lasting antisecretory action in pylorus ligated rats. The inhibitory potency of IT-066 given subcutaneously for gastric acid secretion was 1285 and 44 times higher than for cimetidine and famotidine, respectively. The duration of the inhibitory action of IT-066 was significantly longer than that of famotidine and cimetidine. In pylorus ligated rats, IT-066 showed almost 20 times higher potency than omeprazole with intraduodenal administration, and almost the same duration of action as omeprazole with one tenth the dose in oral administration. IT-066 showed a powerful protective effect on various experimental ulcer models. The potency of IT-066 administered subcutaneously was significantly higher compared with that of cimetidine, famotidine and omeprazole. IT-066 given orally also showed a more powerful antiulcer effect than cimetidine and omeprazole, and was comparable with that of famotidine in restraint and water immersion stress and cold-stress plus indometacin induced ulcer models in rats. These results suggest that IT-066 has powerful and long lasting antisecretory and antiulcer effects and is a useful antisecretory drug for treatment of peptic ulcer diseases. 相似文献
15.
N-(3-[3-(1-Piperidinylmethyl)phenoxy]propyl)-acetoxyacetamide++ + hydrochloride (TZU-0460) was compared with cimetidine for the effects on gastric acid secretion in dog and rat and on ulcer formation in rat. TZU-0460 as well as cimetidine, given i.v. or p.o., produced a dose-dependent inhibition of acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain gastric pouch dogs and gastric lumen-perfused rats. In dog, the relative potencies of TZU-0460 to cimetidine, given p.o. and i.v., were 6.2 and 5.1, respectively, in acid secretion stimulated by histamine, and those gained by i.v. route were 3.5 by pentagastrin and 4.2 by carbachol. In rat, however, relative potencies of TZU-0460 to cimetidine, given i.v., were 2.8, 2.2 and 1.6 in acid secretion stimulated by histamine, pentagastrin and carbachol, respectively. TZU-0460, given p.o., prevented the formation of gastric ulcers induced by exposure to stress, pylorus-ligation, both pylorus-ligation and acetylsalicyclic acid, indometacin or reserpine in rats. TZU-0460 was about twice as active as cimetidine on these experimental models of gastric ulcers. TZU-0460, given p.o., prevented the formation of duodenal ulcer induced by cysteamine in rats, whereas cimetidine failed to prevent it significantly. 相似文献
16.
S Yano Y Kimura S Horie K Ito N Yamada M Mizuno K Watanabe 《Japanese journal of pharmacology》1990,52(2):287-293
KW-5805, 5-[2-(diethylamino)ethyl]amino-5,11-dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride, is a new tricyclic compound with antiulcer activities. Its effect on stimulated gastric acid secretion was investigated in the perfused stomach of anesthetized rats. KW-5805 at 0.3-10 mg/kg, i.v., dose-dependently inhibited gastric acid secretion stimulated by 2-deoxy-D-glucose (2-DG). On the other hand, the compound at 10-20 mg/kg, i.v., exerted a moderate decrease in gastric acid secretion stimulated by bethanechol; and at 10 mg/kg, i.v., it produced no change in gastric acid secretion evoked peripherally by vagal electrical stimulation. When applied intracerebroventricularly at 1-5 micrograms/rat, this compound dose-relatedly reduced gastric acid secretion stimulated by 2-DG. Three main metabolites (KF-10504, KF-9530 and KF-10847) of KW-5805 at 1 mg/kg, i.v., caused no significant decrease in gastric acid secretion stimulated by 2-DG. Doxepin, a tricyclic compound, definitely depressed the 2-DG stimulated gastric acid secretion at 1 mg/kg, i.v. It is suggested that intravenous administration of KW-5805 inhibits gastric acid secretion stimulated by 2-DG, mainly via centrally mediated mechanisms, and that biotransformation of KW-5805 to the metabolites contributes little to the development of the antisecretory effect. 相似文献
17.
Effect of OPC-12759, a novel antiulcer agent, on chronic and acute experimental gastric ulcer, and gastric secretion in rats 总被引:3,自引:0,他引:3
K Yamasaki H Ishiyama T Imaizumi T Kanbe Y Yabuuchi 《Japanese journal of pharmacology》1989,49(4):441-448
The antiulcer effects of OPC-12759, a novel antiulcer agent were compared with those of cetraxate in various experimental ulcer models and on gastric secretion in rats. OPC-12759 (0.3-30 mg/kg, b.i.d., p.o.) significantly accelerated the healing rate of acetic acid-induced gastric ulcer in a dose-dependent manner, while cetraxate did not. When administered orally at 0.3-30 mg/kg, b.i.d., for 7 days, pretreatment with OPC-12759 (0.3-30 mg/kg, b.i.d., p.o.) prevented the formation of acute gastric ulcers, induced by: restraint water immersion stress, aspirin, indomethacin, histamine, serotonin, platelet activating factor (PAF) and DDC. Cetraxate showed antiulcer activity against a part of the OPC-12759-positive gastric ulcer models. Given intraperitoneally at the single dosing range of 10-100 mg/kg, OPC-12759 inhibited the formation of these acute gastric ulcer models. OPC-12759 administered orally at 0.3-30 mg/kg, b.i.d., for 7 days did not inhibit basal gastric secretion in pylorus ligated rats. The results indicated that OPC-12759 possesses wide spectrum antiulcer activity as compared with cetraxate. 相似文献
18.
Mori J Hayashi T Iwashima M Matsunaga T Saito H 《Biological & pharmaceutical bulletin》2006,29(6):1197-1201
Previously, we reported the anti oxidative and anti viral effects of plastoquinones (compounds 1, 2) extracted from the seaweed Sargassum micracanthum (KUETZING) ENDLICHER and a new chromene compound (compound 3), which was converted from the plastoquinones. Recently, we have also demonstrated the antiulcer effects of these compounds and assessed the effects using a rat model of acute gastric lesion and fundus strips isolated from rats. In hydrochloric acid/ethanol rat ulcer tests: 1) oral administrations of compounds 1, 2, and 3 1-10, 3-30 and 10-30 mg/kg, respectively, and omeprazole 3-30 mg/kg showed dose-dependent antiulcer effects: 2) the antiulcer effects after intraduodenal administration of the respective compounds at the dose of 30 mg/kg were found to be significant: and 3) a decrease in the hexosamine level of the gastric mucosa was slightly improved by oral administration of compounds 1, 2, and 3 30 mg/kg. In indomethacin-induced gastric ulcer tests, the antiulcer effects of compounds 1, 2, and 3 10 mg/kg (p.o.) were not significant. Compounds 1, 2, and 3 showed slight contracting effects on the fundus isolated from rats and these effects were inhibited by pretreatment with AH6809, an inhibitor of prostaglandin DP, EP(1), and EP(2) receptors. These results suggest that the protection of the mucosa via endogenous prostaglandins might be related to the antiulcer effects of compounds 1, 2, and 3. 相似文献
19.
1. Propyl-methylenedioxyindene (pr-MDI) is an intracellularly acting calcium antagonist with H2-receptor blocking properties. Stimulus-secretion coupling is inhibited by much lower concentrations of pr-MDI than is excitation-contraction coupling. 2. Since the processes leading to gastric ulceration are calcium-dependent, the aim of this study was to determine if pr-MDI could provide useful antiulcer activity at doses below those required to produce cardiovascular effects. 3. The antiulcer activity of pr-MDI (10-30 mg/kg) was examined in the cold (4 degree C)/restraint (3 hr) stress-induced ulcer model in male rats, and compared with the effects of the H2-blocker cimetidine (10-30 mg/kg) and the calcium channel blocker verapamil (11-32 mg/kg). The drugs were administered intraperitoneally 10 min prior to the cold/restraint stress. 4. All three drugs significantly reduced the number of ulcers and the cumulative length of ulcerated stomach surface in a roughly dose-dependent and equivalent manner. However, whereas the antiulcer doses of verapamil were extremely high, those of pr-MDI were one-sixth to one-half of its antiarrhythmic ED50 in rodents. 相似文献
20.
The effect of metiamide on reserpine-induced gastric ulcers and on gastric secretion during 6 h after ip administration was investigated in conscious intact rats and in rats with chronic gastric fistula. Reserpine, 3 mg/kg ip increased substantially the concentration of gastric acid in the first 4 h. Metiamide given every 3 h in a low dose (0.01 mumol/kg) intensified reserpine-induced gastric ulcers and also significantly increased the reserpine-induced acid concentration and output. In larger doses, (50-100 mumol/kg) metiamide considerably diminished gastric ulcer development and decreased gastric acid concentration. Given every 2 h metiamide in doses of 50-100 mumol/kg almost completely abolished gastric ulcer formation and markedly reduced the secretion of gastric acid in reserpinized rats. Anti-ulcer effect of metiamide was stronger than its antisecretory action, suggesting also the antiulcer action of metiamide other than inhibition of acid secretion. The results suggest that in conscious rats histamine H2-receptors are involved in reserpine-induced gastric ulcer development and gastric acid secretion. The antiulcer effect of metiamide may in part depend on its antisecretory action. 相似文献