metiamide and Stomach-Ulcer

Topics: Burimamide; Chemical Phenomena; Chemistry; Cimetidine; Duodenal Ulcer; Esophagitis, Peptic; Gastric Acid; Gastrins; Gastrointestinal Hemorrhage; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Hypersensitivity; Intrinsic Factor; Kinetics; Malabsorption Syndromes; Metiamide; Pancreas; Pepsin A; Ranitidine; Receptors, Histamine H2; Stomach Ulcer; Stress, Psychological; Zollinger-Ellison Syndrome

Development of histamine H2-receptor antagonists has enhanced the understanding of histamine physiology and pharmacology. The effect of H2-receptor antagonists on gastrointestinal physiology has been studied extensively. These compounds inhibit gastric acid secretion in response to all known secretagogues and, in contrast to anticholinergic drugs, markedly inhibit food-stimulated acid secretion in duodenal ulcer patients. The relative roles of H2-receptor antagonists, anticholinergic drugs and antacids in the treatment of duodenal ulcer remain to be defined. Cimetidine currently is under investigation for the treatment of duodenal ulcer, gastric ulcer, reflux esophagitis, gastrointestinal bleeding and hypersecretory states. Although the long-term safety of cimetidine has not been established, in short-term clinical trials there have been no significant subjective or objective side-effects. Assuming that toxic effects do not develop, H2-receptor antagonists should improve the treatment of acid-peptic disease.

Topics: Cimetidine; Cyclic AMP; Duodenal Ulcer; Esophagitis, Peptic; Gastric Juice; Gastrins; Gastritis; Gastrointestinal Hemorrhage; Histamine; Histamine H2 Antagonists; Humans; Intrinsic Factor; Metiamide; Pepsin A; Stomach Ulcer

Topics: Agranulocytosis; Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastric Juice; Guanidines; Histamine H1 Antagonists; Humans; Imidazoles; Metiamide; Peptic Ulcer; Receptors, Drug; Stomach Ulcer

Conservative management of peptic ulcer relies on the use of drugs as an adjuvant to the time-honored measures of avoiding stress, reducing gastric secretion, and regulating the diet. Alkalies neutralize acid and anticholinergic drugs partly inhibit secretion.. Both are widely used but are often inadequate to control symptoms. Carbenoxolone appears to have a more specific effect in promoting healing of gastric ulcers and has now been used for 15 years. Its role in the treatment of gastric ulcer can be critrically examined, particularly in relation to how this influences surgical management. Recently introduced compounds know as histamine H2-receptor antagonists have a profound effect in inhibiting gastric secretion. Early experience in patients with duodenal ulcer indicated the efficacy of these compounds in promoting healing. These potent new drugs are likely to influence strongly the management of patients with duodenal ulcer, and this may affect the indications for surgery.

Topics: Animals; Carbenoxolone; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Diffusion; Duodenal Ulcer; Gastric Juice; Histamine H2 Antagonists; Humans; Methylhistamines; Metiamide; Peptic Ulcer; Stomach Ulcer; Triterpenes

In two controlled trials, involving 75 patients, on the prevention of bleeding from gastric erosions in fulminant hepatic failure, antacids given four-hourly had no significant effect. Only 35% of intragastric pH recordings taken at two-hourly intervals in the treated group were maintained above 5 with the doses used, whereas this could be consistently achieved with the histamine H2-receptor antagonists, metiamide and cimetidine. In the group receiving these drugs only 1 patient out of 26 bled, compared with 13 (54%) of the controls, a highly significant difference. Blood-transfusion requirements were significantly less in those treated with H2-receptor antagonists.

Topics: Antacids; Clinical Trials as Topic; Drug Evaluation; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Guanidines; Hepatic Encephalopathy; Histamine H2 Antagonists; Humans; Imidazoles; Metiamide; Peptic Ulcer Hemorrhage; Stomach Ulcer

Prostaglandins of the E series have been shown, both in animals and humans to produce gastrointestinal antisecretory and antiulcer effects. Enprostil, a modified allenic prostaglandin E was found to be a highly potent inhibitor of gastric HCl secretion in a variety of species. In rats, in which both the pylorus and esophagus were ligated, p.o. ED50 values and 95% CL for inhibiting acid secretion evoked by histamine, pentagastrin and carbachol were 9.9 (6.7-15), 40 (11-145) and 0.83 (0.78-0.89) micrograms/kg, respectively. In inhibiting histamine-evoked acid secretion, enprostil was more potent when administered p.o. than when injected into the duodenum or s.c. When enprostil was injected directly into the pouch of Heidenhein dogs, intense antisecretory activity occurred, ED50 = 0.9 (0.7-1.1) micrograms/kg, whereas, when given p.o. to the main stomach the ED50 was 6.6 (3.2-13.6) micrograms/kg. Administration of cimetidine either p.o. or to the pouch resulted in virtually identical ED50 values, viz., 2.9 and 3.1 mg/kg. Enprostil also inhibited dimaprit- and pentagastrin-induced acid secretion in cats with permanent gastric fistulae. The oral ED50 values for inhibiting acid secretion evoked by these two secretagogues were 2.5 (1.4-4.3) and 0.8 (0.5-1.5) micrograms/kg, respectively. Enprostil was extremely potent in preventing indomethacin plus "cold stress" ulcers in rats. When given orally the ED50 was 0.61 (0.31-1.22) and s.c. it was 22 (9.0-52) micrograms/kg. It was also highly potent in preventing cysteamine-induced duodenal ulcers when given p.o., ED50 = 20 (17-23) micrograms/kg. Thus, enprostil is a highly potent antisecretory and antiulcer agent. It appears to act topically; directly at gastric mucosal sites.

Topics: Animals; Atropine; Cardiovascular System; Cats; Cysteamine; Dinoprostone; Dogs; Duodenal Ulcer; Enprostil; Fasting; Female; Gastric Emptying; Gastric Mucosa; Male; Metiamide; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer; Uterine Contraction

Four experiments were conducted to evaluate the effect of diet and the administration of H2-antagonists in feed on gastric ulcer formation and performance of growing-finishing swine. Pigs receiving a finely ground diet (less than lmm) grew faster (.73 vs .68 kg/d, P less than .01) and had better feed utilization (3.47 vs 3.76, P less than .01) than pigs receiving a cracked corn-based diet. Incidence of ulcers in the esophageal region of the stomach of pigs fed the finely ground diet was greater (P less than .01) than in pigs fed cracked corn. The average daily gain of pigs receiving the finely ground diet was inversely related to ulcer incidence (r = .403, P less than .01, df = 59). The addition of 5, 10, 20 or 100 ppm of the H2-antagonist, metiamide, or 6, 18 or 54 ppm of SK&F 93479 to the finely ground diet did not improve pig performance or affect the incidence of gastric ulceration. The addition of 2, 6 and 18 ppm of SK&F 93479 to a corn-soy diet containing 4.5% alfalfa meal caused a reduction in gastric ulceration (P less than .05) and improved feed utilization by 3.2% (P less than .05). These data suggest that finely ground diets improve the performance of growing-finishing swine, but increase the incidence of ulcers in the esophageal region of the stomach. Severe gastric ulceration adversely affects swine performance. Feeding H2-antagonists does not reduce the ulcerogenic properties of finely ground diets, suggesting factors other than gastric acid secretion are involved in ulcerogenesis. The use of H2-antagonists in corn-soy diets improves feed utilization and reduces ulceration.

Topics: Animal Feed; Animals; Disease Models, Animal; Female; Food Additives; Histamine H2 Antagonists; Male; Metiamide; Particle Size; Pyrimidinones; Stomach Ulcer; Swine; Swine Diseases; Thiourea

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.

Topics: Animals; Gastric Acid; Male; Metiamide; Pepsin A; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Histamine H2; Reserpine; Stomach Ulcer; Thiourea; Time Factors

Topics: Acetonitriles; Albuterol; Animals; Anti-Ulcer Agents; Carbenoxolone; Gastric Mucosa; Indomethacin; Male; Metiamide; Mucus; Pyridines; Rats; Stomach Ulcer; Stress, Physiological

In order to investigate the cytoprotective action of 16-16-dimethyl-prostaglandin E2 (16-16D), we studied its effect on sacs of isolated amphibian gastric mucosa known to ulcerate with high frequency in the absence of nutrient HCO3-. The actions of 16-16D, 2.85 X 10(-6) M, were also studied in an in vitro chamber. The incidence of ulceration in HCO3- -free nutrient media containing 10(-4) M histamine was significantly reduced by 16-16D. When artificial gastric juice (AGJ) was instilled into the lumen of the sac, protection occurred only after a pretreatment period of 60 min. Cytoprotection was not observed when active secretion of H+ was inhibited with 10(-3) M metiamide, and AGJ was placed in the lumen of the sac. In open sheets of fundus stimulated with 10(-4) M histamine, 16-16D did not influence H+ secretion. Isc was significantly higher than in control tissues. We conclude that 16-16D is cytoprotective in amphibian gastric mucosa by an action independent of changes in acid secretion or in blood flow. In addition, our studies suggest that 16-16D may increase the availability to the surface cells of nutrient HCO3- produced by actively secreting oxyntic cells.

Topics: 16,16-Dimethylprostaglandin E2; Acid-Base Equilibrium; Animals; Anura; Buffers; Gastric Mucosa; Histamine; In Vitro Techniques; Male; Metiamide; Prostaglandins E, Synthetic; Rana catesbeiana; Stomach Ulcer; Time Factors

In in vitro bullfrog fundic mucosa inhibited with 10(-3) M metiamide and exposed to a luminal pH of 2 a progressive slow decline in potential difference (PD) and short-circuit current (Isc) and a rise in resistance (R) were observed when the nutrient solution (N) contained 18 mM HCO3(-), but these changes were restored by an N containing 50 mM HCO3(-). Substitution of PO4(3-) or N-tris(hydroxymethyl)-methyl-2-aminoethanesulfonic acid for NHO3(-) in N caused a rapid drop in PD and Isc in inhibited tissues, changes that could be prevented by 10(-4) M histamine. Ulceration occurred more frequently in metiamide-inhibited gastric sacs exposed to artificial gastric juice with an N of 18 mMHCO3(-) than with 50 mM HCO3(-), but histamine prevented ulceration in the 18 mM HCO3(-) solution. JnetCl approximated Isc under most experimental conditions in inhibited mucosa and was reduced dramatically as were both Jn leads to sCl and Js leads to nCl when HCO3(-) was removed from N. In histamine-stimulated tissues, removal of nutrient HCO3(-) did not influence Cl- transport. Our results are consistent with the proposal that HCO3(-) in N supports normal Cl- flux and that the alkaline tide of actively secreting oxyntic cells can do the same in the absence of ambient HCO3(-).

Topics: Animals; Bicarbonates; Cell Membrane Permeability; Chlorides; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Histamine; Membrane Potentials; Metiamide; Rana catesbeiana; Stomach Ulcer

The ability of two types of gastric acid inhibitor to reverse established gastric mucosal barrier damage was studied in canine Heidenhain pouches. A model of established barrier damage was prepared and validated by perfusing Heidenhain pouches with an acid saline solution containing 20 mmoles of aspirin for 2 hours (damage period) and then perfusing with acid saline alone for a third hour (recovery period). Increases in gastric mucosal permeability to H+ and Na+ produced in the damage period still were present and were significant in the recovery period. In subsequent experiments the effect of topically applied prostaglandin E2 and 15-methyl prostaglandin E2 and intravenously administered prostaglandin E2, 15-methyl prostaglandin E2, and Metiamide on the recovery period permeability was studied. Topical application of the prostaglandins and intravenous Metiamide had no effect on the increased permeability. Intravenously administered prostaglandins returned the permeability to normal and therefore reversed established barrier damage. This effect may have important therapeutic implications in acute gastric mucosal lesions.

Topics: Administration, Topical; Animals; Aspirin; Cell Membrane Permeability; Disease Models, Animal; Dogs; Female; Gastric Juice; Gastric Mucosa; Histamine; Injections, Intravenous; Metiamide; Prostaglandins E, Synthetic; Regression Analysis; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Thiourea

The effects of atropine, mepyramine, metiamide or NaHCO3 on gastric ulceration, gastric secretion and gastric mast cell degranulation were studied in stressed pylorus-occluded rats. The influence of dexamethasone pretreatment on stress ulcers in animals without pylorus occlusion (intact rats) was also examined. Stress produced a high glandular lesion incidence and ulcer index, and markedly lowered gastric secretion and glandular wall mast cell counts. Injected 0.5 h before stress, atropine, mepyramine or metiamide strongly antagonised ulceration. Atropine or metiamide, but not mepyramine, reduced gastric secretion. Only atropine prevented stress-induced mast cell changes. NaHCO3, given intragastrically before stress, did not prevent ulceration or mast cell degranulation despite complete neutralisation of gastric acid. Dexamethasone-induced gastric mucosal mast cell depletion could reduce stress ulceration. The findings show that stress degranulates stomach mast cells via a cholinergic pathway; released histamine from this source is largely responsbile for gastric ulceration through H1- and H2-receptor effects. Histamine H2-receptor-mediated gastric acid may play only a small contributory role in stress ulcers in rats. The antiulcer mechanisms of histamine H1- and H2-receptor blockade are discussed.

Topics: Animals; Atropine; Bicarbonates; Dexamethasone; Male; Mast Cells; Metiamide; Parasympathetic Nervous System; Pylorus; Pyrilamine; Rats; Receptors, Histamine H1; Receptors, Histamine H2; Stomach; Stomach Ulcer; Stress, Physiological

Intramural pH of the gastric mucosa was measured using a microelectrode technique in rabbit gastric pouches under different secretory conditions and luminal acidity. Exposure of spontaneously secreting or metiamide-treated fundic pouches to a relatively high concentration of luminal acid. HCl 120 mM, for 60 min, led to a marked net loss of luminal H+ which was associated with a significant decrease in the intramural pH (7.28 +/- 0.09 to 6.88 +/- 0.10 and 7.23 +/- 0.07 to 6.99 +/- 0.09, respectively). A linear relationship was observed between the rates of net disappearance of luminal acid and the intramural pH. All 10 spontaneously secreting and five metiamide-treated pouches had superficial mucosal erosions. In contrast, when fundic pouches were exposed to luminal acid in histamine-treated animals, the net loss of luminal H+ was negligible and the intramural pH remained at its base-line level (7.25 +/- 0.07). Histamine stimulation without acid in the lumen caused a small but insignificant increase in the intramural pH (7.27 +/- 0.03 to 7.39 +/- 0.05). Only three of the eight histamine-treated fundic pouches had lesions. In the antral pouches the intramural pH changes in response to exposure to luminal acid were smaller and histamine treatment did not influence the intramural pH. None of the antral pouches had lesions. The results suggest that acidification of the tissue by the diffusion of luminal acid may be an important factor in the pathogenesis of acute gastric ulceration. The acid secretory state of the gastric mucosa can significantly influence the acid-base balance in the mucosa and thus modify its response to acid diffusing from the lumen. Histamine stimulation protected the gastric mucosa by improving its buffering capacity and/or otherwise decreasing the diffusion of H+ from the lumen into the mucosa.

Topics: Animals; Chlorides; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Histamine; Hydrogen-Ion Concentration; Metiamide; Microelectrodes; Rabbits; Sodium; Stimulation, Chemical; Stomach Ulcer

Topics: Animals; Bile Acids and Salts; Dogs; Gastric Mucosa; Ischemia; Metiamide; Stomach Ulcer; Thiourea

Stress produced severe mucosal ulcers, increased mucosal microcirculation and lowered mast cell counts in the glandular wall of rat stomachs. Mepyramine i.m. or metiamide i.p. effectively prevented both ulceration and microcirculatory changes but not stress-reduced mast cell counts.

Topics: Aminopyridines; Animals; Dose-Response Relationship, Drug; Gastric Mucosa; Humans; Male; Mast Cells; Metiamide; Microcirculation; Pyrilamine; Rats; Receptors, Histamine; Stomach Ulcer; Stress, Psychological; Thiourea

Topics: Animals; Feeding Behavior; Food Deprivation; Male; Metiamide; Rats; Stomach Ulcer; Thiourea; Time Factors; Water Deprivation

The capacity of the stomach to resist the effects of highly acid solutions was assessed by comparing the effects of such solutions on spontaneously secreting, stimulated, and inhibited gastric mucosae of rabbits in vivo and frogs in vitro. Exposure of unstimulated resting mucosa to HC1, 120 mM, for 60 minutes produced superficial erosions in all rabbits, whereas such lesions were observed in only one of ten animals stimulated with histamine. Metiamide obviated the protective effect of histamine against ulcerations even though it did not reduce H+ secretion to zero. Exposure of inhibited isolated frog fundic mucosa to HC1 resulted in significant deterioration of electrical parameters, suggesting impairment of active transport processes and increased tissue permeability. These data are consistent with the hypothesis that actively secreting gastric mucosae from two species resist injury to exogenous acid more effectively than do resting or inhibited tissues, perhaps in part as a result of a greater alkaline tide.

Topics: Animals; Burimamide; Diffusion; Gastric Juice; Gastric Mucosa; Histamine; Hydrogen-Ion Concentration; In Vitro Techniques; Male; Metiamide; Rabbits; Rana catesbeiana; Secretory Rate; Stomach Ulcer

In rats under either mild stress (= controls) or severe stress (= restraint) gastric secretion (acid; pepsin, volume), mucosal blood flow, serum gastrin and ulcer formation were evaluated without and with additional infusion of a low dose (0.25 mg/kg.h) metiamide over an 8 h experimental period. Calculated constants of dose-response characteristics for acid output in this species are: Km = 1.41 +/- 0.36 mg/kg.h; Vmax = 94.4 +/- 11.0 per cent. Restraint depresses markedly secretion and microcirculation, but stimulates ulcer formation and raises serum gastrin. In controls, metiamide inhibits secretion and ulcer index significantly, but leaves mucosal blood flow and gastrin unaltered. In contrast, with restraint and metiamide, ulcer index was not improved, whereas mucosal blood flow was restored to almost control levels. Therefore, H2-receptor blockers, in addition to inhibition of secretion, may interfere with microcirculation either directly or by secondary release of yet unknown mediator substance(s), depending on the prevailing tissue environment.

Topics: Acids; Animals; Dose-Response Relationship, Drug; Gastric Mucosa; Male; Metiamide; Pepsin A; Rats; Regional Blood Flow; Restraint, Physical; Stomach Ulcer; Thiourea

Restrain stress in rats inhibits gastric secretion and microcirculation. Secretion is further inhibited by metiamide, but mucosal blood flow is restored to normal. During stress the ulcer incidence is high, lower with prophylactic administration of metiamide and least with the latter and preserved gastroduodenal acid transit. No therapeutic metiamide effect can be detected.

Topics: Aminopyrine; Animals; Gastric Juice; Gastric Mucosa; Male; Metiamide; Microcirculation; Pepsin A; Rats; Receptors, Histamine; Receptors, Histamine H2; Restraint, Physical; Stomach Ulcer; Stress, Physiological; Thiourea

Prevention of acute gastric erosions with histamine H2-receptor blocking agents suggests that these drugs may improve the ability of the gastric mucosa to maintain electrical, ionic, and protein concentration gradients. In 5 awake mongrel dogs, transmural potential difference, ion fluxes, and protein loss were measured across Heidenhain pouches topically exposed to isotonic solutions containing either 80 mM HCl or 80 mM HCl plus 20 mM sodium taurocholate (BS). The dogs received an intravenous infusion of either saline (as a control) or the H2 antagonist metiamide, 10 mumoles per kg-hr. Metiamide increased the H+ clearance rate found after acid test solution exposure but had no significant effect on potential difference or ion fluxes. H2 antagonism decreased the protein loss but not the increase in cation permeability due to BS. Net H+ loss actually increased, which, along with a decrease in Cl- gain, suggests inhibition of acid secretion by metiamide in BS-exposed gastric mucosa. These effects of metiamide point to histamine as a likely mediator of the gastric mucosal damage due to BS.

Topics: Animals; Cell Membrane Permeability; Dogs; Gastric Acidity Determination; Gastric Mucosa; Hydrochloric Acid; Metiamide; Potassium; Sodium; Stomach Ulcer; Taurocholic Acid; Thiourea

Topics: Histamine H1 Antagonists; Humans; Metiamide; Stomach Ulcer; Thiourea

Topics: Antacids; Drug Evaluation; Guanidines; Humans; Imidazoles; Metiamide; Stomach Ulcer; Thiourea

Topics: Animals; Aspirin; Corticosterone; Female; Histamine; Histamine H1 Antagonists; Histamine Release; Metiamide; Pyrilamine; Rats; Receptors, Drug; Stomach Ulcer; Stress, Physiological

Water-immersion stress for 7, 14, or 20 hr consistently induced linear or punctate stress ulcers (mucosal erosions) in the corpus of the stomach in intact rats. When the pylorus of the stomach had been ligated prior to stressing, the stress ulcers changed their morphological feature (mainly punctate and in one place elongated) and location (both in corpus and antrum). Histologically, the stress ulcer developed in the proximal antrum of pylorus ligated rats and penetrated into the muscularis mucosa. Sodium bicarbonate, chlorpromazine, hexamethonium, atropine, metiamide, and bilateral vagotomy markedly inhibited the stress ulcers which developed in the pylorus-ligated rats. Phentolamine and propranolol hardly affected the development of stress ulcers. Amylopectine evoked a new type of stress ulcer in the corpus when it was given to the pylorus-ligated rats.

Topics: Amylopectin; Animals; Atropine; Bicarbonates; Chlorpromazine; Disease Models, Animal; Gastric Mucosa; Hexamethonium Compounds; Immersion; Ligation; Male; Metiamide; Phentolamine; Propranolol; Pylorus; Rats; Stomach Ulcer; Stress, Physiological; Time Factors

Because of evidence that Metiamide, an H2-receptor antagonist, strongly inhibits gastric acid secretion, the present study was designed to test the hypothesis that Metiamide will prevent bile salt-induced stress ulcers during hemorrhagic shock. Forty dogs were bled and maintained for 4 1/2 hr at a mean blood pressure of 40 to 50 mm Hg. In group A, 10 dogs received 300 mg of Metiamide orally 45 min before bleeding and 10 dogs received normal saline. The pylorus was occluded before bleeding and 100 ml of 15 mM bile salt were instilled into the stomach and aspirated at the end of 4 1/2 hr. At the time the animal was killed after 48 hr, no ulcers were seen in the stomachs of dogs treated with Metiamide. Sixty per cent of the dogs in the untreated group developed multiple gross ulcers. In group B the effect of Metiamide on the disappearance rate of H+ ion was measured by instillation of 50 mM HCl + 15 mM bile acid. No difference was noted in the rate of H+ ion disappearance between Metiamide-treated and control dogs. Also, in 5 normotensive dogs the rate of H+ ion disappearance was measured before and after treatment with Metiamide, and the loss of H+ was identical for both periods. Metiamide was effective in preventing stress ulcer in this experimental model. The protective effect of Metiamide is probably due to its inhibitory effect of H+ ion secretion.

Topics: Administration, Oral; Animals; Dogs; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Humans; Infusions, Parenteral; Metiamide; Shock, Hemorrhagic; Stomach Ulcer; Stress, Psychological; Thiourea

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Gastric Juice; Gastric Mucosa; Ischemia; Male; Metiamide; Pepsinogens; Rats; Stomach Ulcer; Stress, Physiological; Thiourea

This study has examined the inhibition produced by metiamide on the gastric secretion of acid and pepsin in 13 patients with duodenal and three with gastric ulcer. The effect of metiamide on the response to a range of doses of pentagastrin in three normal individuals was determined, as was the interaction of metiamide and atropine on prolonged basal secretion. Metiamide inhibited the secretion of acid more than pepsin and the gastric secretion of patients with gastric ulcer more than duodenal ulcer. Metiamide inhibited both the maximal secretory response attainable with pentagastrin and decreased the sensitivity to pentagastrin. Atropine augmented and prolonged the action of metiamide.

Topics: Atropine; Dose-Response Relationship, Drug; Drug Synergism; Duodenal Ulcer; Gastric Juice; Humans; Metiamide; Pentagastrin; Pepsin A; Secretory Rate; Stomach; Stomach Ulcer; Thiourea

Topics: Adrenal Cortex Hormones; Animals; Cold Temperature; Female; Metiamide; Rats; Salicylates; Stomach Ulcer; Stress, Physiological

Metiamide was given to patients with peptic ulcer or oesophagitis in a pilot study to establish the therapeutic value of the drug. Administration of metiamide resulted in relief of pain within a week in the majority of patients. Healing of duodenal and gastric ulcers was observed.

Topics: Duodenal Ulcer; Esophagitis; Gastric Acidity Determination; Gastric Juice; Humans; Metiamide; Nausea; Pain; Pancreatitis; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Thiourea; Time Factors

Forty rats were housed in standard activity wheel cages and fed for only 1 hr per day. The animals were equally divided into 4 groups that received either saline, 12.5 mg/kg, 25.0 mg/kg or 50.0 mg/kg of metiamide, an H2 receptor antagonist, 3 times a day. All animals died within 11 days and all demonstrated significant gastric lesions in the glandular fundus of the stomach. The 50.0 mg/kg dosage group, however, demonstrated significantly fewer ulcers than the saline animals and the lesions that did occur were significantly smaller than those noted in the control animals. Several hypotheses were offered to explain these results which took into account metiamide's effects on gastric secretion and motor activity. It was suggested that secretion of acid may be an important contributing factor in the formation of gastric ulcers in animals subjected to the "activity-stress" procedure.

Topics: Animals; Disease Models, Animal; Food Deprivation; Gastric Juice; Male; Metiamide; Rats; Stomach Ulcer; Stress, Physiological; Thiourea

Topics: Animals; Dogs; Gastric Juice; Metiamide; Shock, Hemorrhagic; Stomach Ulcer; Stress, Physiological; Thiourea