metiamide and Duodenal-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: Burimamide; Cimetidine; Creatinine; Duodenal Ulcer; Esophagitis, Peptic; Gastric Juice; Gastritis; Guanidines; Humans; Metiamide; Peptic Ulcer; Receptors, Histamine; Transaminases; Zollinger-Ellison Syndrome

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

Cimetidine inhibits basal and nocturnal acid secretion and acid secretion stimulated by histamine, pentagastrin, caffeine, insulin, sham feeding, and food. Cinetidine (300 mg) inhibits basal acid secretion in duodenal ulcer patients by 95% for at least 5 hr. When taken at bedtime, cimetidine inhibits nocturnal acid secretion by greater than 80% for most of the night. Cimetidine markedly inhibits food-stimulated acid secretion and is more effective than anticholinergic drugs. However, to get adequate suppression of food-stimulated acid secretion throughout the day, cimetidine should be given with each meal. Cimetidine has no effect on nocturnal serum gastrin concentration, but, when stimulated by food, serum gastrin concentration is higher after cimetidine than after placebo.

Topics: Cimetidine; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Glycopyrrolate; Guanidines; Humans; Metiamide; Quaternary Ammonium Compounds; Time Factors

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

Cimetidine markedly inhibits gastric acid secretion, but from the therapeutic point of view it is important to know whether concurrent treatment with an anticholinergic increases its effect. This possibility has been investigated by measuring the 24 h intragastric acidity and nocturnal output of acid in four duodenal ulcer patients, each receiving on separate occasions cimetidine 1 g/day and placebo, atropine 2-4 mg/day and placebo, cimetidine and atropine, or two placebos. Cimetidine alone decreased mean hourly hydrogen ion activity by 63% of control values, decreased mean hourly hydrogen ion concentration (total acid) by 41%, inhibited nocturnal acid secretion by 83% and resulted in half the nocturnal samples being anacidic. Atropine alone had no effect when compared with control and combined treatment with both drugs was not superior to cimetidine alone. Atropine did not affect the absorption or urinary excretion of cimetidine. Fasting serum gastrin concentrations were not changed by any of the treatments. At the doses studied, the combination of cimetidine with an anticholinergic appears to offer no advantages over treatment with the H2-antagonist alone. Cimetidine is the only potent anti-secretory drug that does not cause acute side-effects and this important advantage would be lost if it were given with a maximal dose of an anticholinergic.

Topics: Administration, Oral; Adult; Atropine; Circadian Rhythm; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Guanidines; Humans; Imidazoles; Male; Metiamide

This paper presents the results of a pilot study to investigate whether the administration of a nocturnal dose of metiamide (the first orally active H2 receptor antagonist) would prevent or delay the relapse of duodenal ulceration after initial ulcer healing. Sixteen patients took part in a double-blind trial to compare metiamide (400 mg) with placebo. Endoscopically confirmed duodenal ulcer relapses occurred in two out of eight on metiamide and six out of eight on placebo. There was a significant prolongation of remission in those in those on the active drug with an apparent reduction in duodenitis.

Topics: Adult; Aged; Clinical Trials as Topic; Duodenal Diseases; Duodenal Ulcer; Enteritis; Humans; Metiamide; Middle Aged; Recurrence; Remission, Spontaneous; Thiourea; Time Factors

A double-blind trial of histamine H2-receptor antagonists and placebo was carried out in 46 patients with endoscopically proven duodenal ulceration. H2-receptor antagonists (metiamide and cimetidine) produced a significantly greater degree of completely healed ulcers and fewer complete failures than placebo. The results of the trial indicate that H2-receptor antagonists promote the healing of ulcers. The action of these compounds would appear to be related to the inhibition of acid secretion. Neither the duration of the illness, rate of recurrence of the ulcers of level of gastric acid secretion materially affected the healing rate in indvidual patients. There were no serious side-effects over the 6-week period of drug administration, but the metiamide was replaced by cimetidine because reports from other centrea indicated that agranulocytosis was associtated with metiamide therapy.

Topics: Antacids; Clinical Trials as Topic; Duodenal Ulcer; Gastric Juice; Histamine H2 Antagonists; Humans; Metiamide; Placebos; Wound Healing

Topics: Burimamide; Clinical Trials as Topic; Duodenal Ulcer; Histamine; Humans; Metiamide; Receptors, Drug

Topics: Clinical Trials as Topic; Duodenal Ulcer; Follow-Up Studies; Humans; Long-Term Care; Metiamide; Recurrence; Thiourea

Metiamide (a histamine H2-receptor antagonist) and propantheline (an anticholinergic) are both inhibitors of gastric acid secretion. We have investigated the effect of gastric acid secretion of blocking the histamine and acetylcholine receptor sites separately and together. There was a statistically significant additive inhibitory effect on pentagastrin-stimulated volume secretion when both drugs were given together. The inhibition of acid output was slightly but insignificantly greater with the combination of drugs than when they were given separately.

Topics: Adult; Depression, Chemical; Drug Therapy, Combination; Duodenal Ulcer; Gastric Juice; Humans; Metiamide; Middle Aged; Pentagastrin; Propantheline; Secretory Rate; Thiourea

The effect of perfusion of the jejunum with acid on the secretion of bicarbonate, trypsin, and bile into the duodenum has been studied in 10 patients with duodenal ulcer and 8 control subjects and compared with the responses to intravenous infusion of secretin and cholecystokinin-pancreozymin (CCK). Both the secretion of bicarbonate and of trypsin into the duodenum were inversely related to the amount of acid dissipated during jejunal transit, so that if all the acid disappeared during transit of a 30-cm segment of jejunum, the pancreas did not secrete. In both groups of subjects, jejunal acidification elicited a relatively greater secretion of bicarbonate than secretion of trypsin or bile into the duodenum, compared with the response to the exogenous hormones. Jejunal acidification also inhibited the secretion of trypsin in response to concurrently administered exogenous hormones by the control subjects but not in patients with duodenal ulcer. We conclude taht the pancreatic response to acid in the human duodenum depends on exposure of the jejunal mucosa to the amounts of acid which are greater than (quite high, but variable) threshold in all subjects. Under the conditions of this study, patients with duodenal ulcer differed from control in lacking an acid-released jejunal inhibitor of the secretion of trypsin by the pancreas.

Topics: Bicarbonates; Bile; Biliary Tract; Cholecystokinin; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Humans; Hydrochloric Acid; Intestinal Secretions; Jejunum; Metiamide; Pancreas; Perfusion; Secretin; Secretory Rate; Trypsin

In a multicentre double-blind trial 68 patients with endoscopically confirmed duodenal ulceration received metiamide (36 patients) or placebo (32 patients) for four weeks. Healing of duodenal ulcers was significantly increased in patients receiving metiamide (67%) compared with those on placebo (25%). There was also an assoicated significant decrease in daytime pain and antacid consumption in those on metiamide.

Topics: Antacids; Clinical Trials as Topic; Drug Evaluation; Duodenal Diseases; Duodenal Ulcer; Enteritis; Humans; Metiamide; Pain; Thiourea

Topics: Bone Marrow; Burimamide; Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Guanidines; Humans; Metiamide; Thiourea

Thirty patients with symptoms of duodenal ulceration were treated for five to eight weeks in a double-blind trial with either metiamide 1 g daily by mouth or a placebo. In the 15 patients receiving metiamide there were significant reductions in nocturnal pain and antacid consumption. Daytime pain was diminished. The results suggest that histamine H2-receptor antagonists are likely to be useful in the medical management of the symptoms of duodenal ulceration.

Topics: Administration, Oral; Antacids; Clinical Trials as Topic; Duodenal Ulcer; Female; Histamine H1 Antagonists; Humans; Male; Metiamide; Pain; Placebos; Thiourea

Topics: Animals; Clinical Trials as Topic; Duodenal Ulcer; Histamine H1 Antagonists; Humans; Metiamide; Thiourea

The clinical, endoscopic, and biochemical effects of metiamide, a histamine H2-receptor antagonist, in therapeutic dosage have been studied in a 28-day open trial in patients with duodenal ulcer disease. A good symptomatic response, combined with a 72% ulcer healing rate was observed. There were small but significant rises in plasma creatinine, serum glutamic oxaloacetic transaminase, and serum lactate dehydrogenase during treatment. Small quantities of amino acids appeared in the urine, and the heart size increased slightly. It is concluded that histamine H2-receptor antagonism may be an important therapeutic approach to duodenal ulcer disease.

Topics: Adult; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation; Duodenal Ulcer; Follow-Up Studies; Humans; Metiamide; Middle Aged; Remission, Spontaneous; Thiourea

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

A patient with systemic mastocytosis, accompanied by gastric hypersecretion and duodenal ulcer, was treated with metiamide followed by daily cimetidine for 44 months. Treatment with cimetidine resulted in healing of the ulcer, without recurrence and marked amelioration of the cutaneous symptoms of mastocytosis. Complete suppression of basal gastric hypersecretion was documented after 33 months of treatment and cimetidine and Vitamin B12 absorption remained normal. Cimetidine reduced the patient's cutaneous response to intradermal histamine without affecting leucocyte histamine release. No cimetidine toxicity was observed. These results indicate that effective long-term control of histamine-induced gastric hypersecretion can be achieved with cimetidine. They suggest that some of the cutaneous symptoms of mastocytosis are mediated via histamine H2 receptors in the skin.

Topics: Adult; Cimetidine; Duodenal Ulcer; Gastric Acid; Guanidines; Humans; Long-Term Care; Male; Metiamide; Osteoporosis; Thiourea; Urticaria Pigmentosa

Insight into the pathogenesis and etiology of experimental duodenal ulceration was sought by studying the modulation of this disease in rats by selective vagotomy, chemical sympathectomy, histamine depletion, histamine H-2 receptor antagonists (eg, metiamide, cimetidine), or endocrine ablations. Gastric secretion was examined in intact and pylorus-ligated animals. The formation of duodenal ulcers induced by the administration of propionitrile or cysteamine was abolished by vagotomy, decreased by sympathectomy, histamine depletion, histamine H-2 receptor antagonists, hypophysectomy, thyroidectomy, or adrenalectomy. Cimetidine and metiamide exerted a dose-dependent antiulcer effect, but metiamide enhanced the mortality of rats given propionitrile or cysteamine. The non-ulcerogen derivative of cysteamine, ethanolamine, did not increase mortality when given in combination with metiamide. The gastric hyperacidity elicited by cysteamine was reduced by metiamide or vagotomy, the latter being more effective in this respect. Thus, the chemically induced duodenal ulcer in rats resembles the human peptic ulcer disease in sensitivity to therapeutic modalities and may serve as an appropriate model to study the role of neural, hormonal, and other factors in the etiology and pathogenesis of this disorder.

Topics: Adrenalectomy; Animals; Castration; Cimetidine; Cysteamine; Disease Models, Animal; Duodenal Ulcer; Gastric Juice; Guanidines; Histamine; Histamine H2 Antagonists; Hypophysectomy; Metiamide; Nitriles; Rats; Sympathectomy; Thiourea; Thyroidectomy; Vagotomy

Twenty-two patients with recurrent ulceration following vagotomy with and without a drainage procedure have been treated with histamine H2-antagonists and followed for up to 3 years. Four of a group of 6 patients responded to a single therapeutic course. Ten of 16 patients assigned to long term maintenance treatment remain symptom-free. Cimetidine may be an alternative to further surgery in the treatment of some patients with recurrent ulceration after vagotomy.

Topics: Adult; Aged; Cimetidine; Duodenal Ulcer; Female; Guanidines; Humans; Male; Metiamide; Middle Aged; Recurrence; Thiourea; Time Factors; Vagotomy

Topics: Adult; Cimetidine; Duodenal Ulcer; Guanidines; Humans; Male; Metiamide; Thiourea; Time Factors

Histamine H2-receptor antagonists (Burimamide, Metiamide and Cimetidine as the most recent generation) may drastically inhibit gastric acid secretion stimulated by histamine, pentagastrin, insulin, 2-deoxyglucose or an intragastrically instilled meal, respectively. This inhibitory action may explain the beneficial effects of H2-antagonists in the treatment of active peptic ulceration. On Cimetidine administered at a usual dosage over a 4--6 week period, serious side-effects must not be expected. At present studies aim to establish a Cimetidine dosage which, on long-term treatment, may reduce ulcer recurrency.

Topics: Burimamide; Duodenal Ulcer; Gastric Juice; Histamine H2 Antagonists; Humans; Mallory-Weiss Syndrome; Metiamide; Peptic Ulcer; Peptic Ulcer Hemorrhage; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastric Juice; Guanidines; Histamine; Humans; Hydrogen-Ion Concentration; Imidazoles; Metiamide; Receptors, Drug

Topics: Adolescent; Adult; Duodenal Ulcer; Gastric Juice; Histamine H1 Antagonists; Humans; Metiamide; Middle Aged; Pentagastrin; Thiourea

A new group of drugs, the histamine2 (H2)-receptor antagonists, act on receptors in the stomach to reduce acid secretion when this is stimulated by histamine, pentagastrin, the vagus nerve or food. The reduction in acid secretion is profound and may approach the degree of reduction brought about by gastric surgery. The H2-receptor antagonist metiamide, administered orally, has been used successfully in the treatment of duodenal ulcer and the Zollinger-Ellison syndrome, but it has been shown to cause agranulocytosis. Trials are in process with an analogue, cimetidine (Tagamet, SKF), which has a different chemical structure from metiamide and has not caused haematological changes in animals or man. These drugs offer the prospect of successful medical management of duodenal ulcer, while a study of their effects on H2-receptors elsewhere in the body may reveal other therapeutic benefits.

Topics: Depression, Chemical; Duodenal Ulcer; Gastric Juice; Histamine H1 Antagonists; Humans; Intestinal Absorption; Metiamide; Neutropenia; Receptors, Histamine; Zollinger-Ellison Syndrome

Serum cholecystokinin (CCK) levels were measured in 10 patients with chronic duodenal ulcers, fasting and at intervals after two standard tests meals (300 ml of 40 mmol/1 phenylalanine solution), one given before and one during H2-receptor blockade with metiamide (200 mg four times a day). Fasting serum CCK levels were lower in all patients during treatment with metiamide (the mean level falling from 306-0 +/- 102-0 (SEM) to 82-1 +/- 23-6 pg/ml after treatment (p less than 0-01)). In contrast, peak serum CCK levels after the meal were not significantly different (7400 +/- 1141 pg/ml before treatment and 7569 +/- 1293 pg/ml on metiamide). We conclude that in duodenal ulcer patients CCK secretion under basal condtions may be in part dependent on stimulation of the small intestinal mucosa by gastric acid, but that, after an amino acid meal, gastric acid secretion is less important in determining the amount of CCK released.

Topics: Cholecystokinin; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Humans; Hydrogen-Ion Concentration; Metiamide; Thiourea; Time Factors

Metiamide was given orally in one dose of 200 mg in 23 sutdies in patients with duodenal ulcer, 4 in the basal state, 11 during histamine infusion, and 8 before insulin hypoglycemia stimulation. In the latter 8 patients insulin was given at another time without metiamide. In 17 studies acid secretion was suppressed by metiamide--up to 75% in the basal state, 53% after histamine, and 80% after insulin. Pepsin secretion was reduced to the same extent as H+ in the histamine studies but not in the basal (57%) or insulin (44%) studies, so that in the latter pepsin/acid ratios were 3-fold greater than in controls. Blood levels of metiamide were measured in 17 studies. In 10 out of 11 who showed inhibition of 40% or more, peak blood levels of metiamide were 0.45 mug/ml to 1.25 mug/ml. In 5 of 6 who did not show inhibition, blood levels were 0.05-0.4 mug/ml; in the sixth it was 0.8 mug/ml. Therefore a critical blood level for suppression of basal or stimulated secretion appears to be approximately 0.45 mug/ml.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Juice; Histamine; Humans; Hypoglycemia; Insulin; Male; Metiamide; Middle Aged; Pepsin A; Thiourea

Topics: Duodenal Ulcer; Follow-Up Studies; Humans; Metiamide; Thiourea

The response of serum gastrin to a meal has been studied in 11 normal subjects and 16 patients with duodenal ulceration. The mean serum gastrin concentration rises after a meal to similar peak values in both normal subjects and duodenal ulcer patients, and fall to basal values with 3 hours in normal subjects. In duodenal ulcer patients the peak concentration is sustained throughout the 3 hour test period, and this response is not affected by the administration of Metiamide. It is concluded that the control of gastrin release is defective in duodenal ulceration, and this may be due to a failure of the antral pH feedback mechanism. Gastrin may be a primary pathogenetic factor in duodenal ulceration.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Male; Metiamide; Middle Aged; Radioimmunoassay; Thiourea; Time Factors

Topics: Animals; Bethanechol Compounds; Duodenal Ulcer; Metiamide; Pentagastrin; Rats; Thiourea

Metiamide an histamine H2-receptors antagonist has been used to treat a case of Zollinger-Ellison syndrome characterized by a long standing diarrhea, an important gastric hypersecretion and a moderatly elevated plasma gastrin but without digestive ulceration. At the dose of 600 mg per day, Metiamide induced a complete suppression of acid secretion, an effect which lasted for 15 days after stopping the drug. Accordingly and since the only finding at time of laparotomy was a small lymph node enlarged with endocrine metastatic tissue, the stomach was left intact and Metiamide pursued. During the first 4 months of chronic administration of Metiamide, acid secretion was maintained at levels below 25 p.cent of initial values. Ulteriorly however, although dosages of Metiamide were increased, acid hypersecretion resumed and a duodenal ulcer developed. Total gastrectomy was then performed 11 months after the beginning of Metiamide. In spite of the failure of Metiamide treatment, the long term follow up of this case of Zollinger-Ellison Syndrome, allowed us to get theoretical and practical informations.

Topics: Adult; Delayed-Action Preparations; Duodenal Ulcer; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine H1 Antagonists; Humans; Male; Metiamide; Middle Aged; Receptors, Drug; Secretin; Secretory Rate; Thiourea; Zollinger-Ellison Syndrome

Topics: Antacids; Drug Evaluation; Duodenal Ulcer; Humans; Metiamide; Middle Aged; Placebos; Thiourea; Time Factors

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

1. The effect of metiamide on gastric acidity in man has been studied. Solutions of hydrochloric acid or glucose were instilled into the stomach and the subsequent rates of gastric secretion and emptying, and the disappearance of acid within the stomach, were measured. 2. Metiamide inhibited the gastric secretory response to the instilled acid and glucose solutions but did not change the overall pattern of emptying of the instilled solutions. 3. During administration of metiamide, there was a net loss of acid from within the gastric lumen. The rate of disappearance of acid from the instilled acid solution was small and not sufficient in magnitude to account for the metiamide-evoked decrease in the concentration of acid secreted in response to pentagastrin. 4. We conclude that metiamide does not inhibit gastric secretion by altering the 'barrier' function of the gastric mucosa.

Topics: Bile Pigments; Chlorides; Duodenal Ulcer; Esophagitis; Gastric Juice; Gastric Mucosa; Humans; Kinetics; Metiamide; Osmolar Concentration; Pentagastrin; Pepsin A; Potassium; Sodium; Thiourea

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