thiourea and Duodenal-Ulcer

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

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

Topics: Agranulocytosis; Bone Marrow; Bone Marrow Cells; Cell Count; Clinical Trials as Topic; Duodenal Ulcer; Female; Histamine H1 Antagonists; Humans; Imidazoles; Leukocyte Count; Leukocytes; Male; Middle Aged; Neutropenia; Sulfides; Thiourea; Time Factors

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

The purpose of the present series of experiments was to measure and compare the effects of an anticholinergic drug (isopropamide) and an antagonist of the histamine H2 receptor (metiamide) on food-stimulated acid secretion. Patients with duodenal ulcers were stimulated by a steak meal, and acid secretion was measured by in vivo intragastric titration. The largest dose of isopropamide that can be taken clinically without producing intolerable side effects (maximum tolerated dose) suppressed food-stimulated acid secretion by 35%. By contrast, metiamide in a 400-mg dose produced no side effects and almost completely abolished food-stimulated acid secretion. A dose-response curve revealed that a 50-mg dose of metiamide was required to suppress food-stimulated acid secretion by 50%. Further studies showed that metiamide and isopropamide are additive in suppressing food-stimulated acid secretion, and that metiamide has no effect on serum gastrin concentration or on gastric emptying.

Topics: Adult; Clinical Trials as Topic; Drug Therapy, Combination; Duodenal Ulcer; Female; Food; Gastric Juice; Gastrins; Gastrointestinal Motility; Histamine; Humans; Imidazoles; Male; Middle Aged; Placebos; Quaternary Ammonium Compounds; Receptors, Drug; Stomach; Sulfides; 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

The effects of intravenous metiamide on the pancreatic exocrine response to intravenous infusion of secretin plus cholecystokinin has been studied in eight patients with duodenal ulceration. The secretion of bicarbonate and water was not altered by metiamide. The secretion of enzymes was significantly less than control during infusion of metiamide. The differences between the pancreatic and gastric responses to metiamide are discussed.

Topics: Bicarbonates; Bile Pigments; Cholecystokinin; Duodenal Ulcer; Fasting; Gastric Juice; Humans; Imidazoles; Injections, Intravenous; Pancreas; Polyethylene Glycols; Secretin; Stomach; Sulfides; Thiourea; Trypsin

Topics: Clinical Trials as Topic; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Histamine H1 Antagonists; Humans; Imidazoles; Placebos; Secretory Rate; Sulfides; Thiourea; Time Factors

Topics: Clinical Trials as Topic; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Gastrins; Histamine H1 Antagonists; Humans; Imidazoles; Male; Middle Aged; Peptones; Receptors, Drug; Sulfides; Thiourea

Topics: Adult; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Histamine H1 Antagonists; Humans; Imidazoles; Middle Aged; Pentagastrin; Secretory Rate; Sulfides; Thiourea

Metiamide greatly reduced pentagastrin-stimulated and overnight secretion of acid and pepsin in 11 patients with duodenal ulcer and virtually abolished gastric secretion in three patients with gastric ulcer. The drug was equally effective when infused intravenously or intraduodenally. A therapeutic trial of Metiamide is warranted in diseases caused or aggravated by excess gastric secretion of acid and pepsin.

Topics: Atropine; Depression, Chemical; Duodenal Ulcer; Duodenum; Gastric Juice; Humans; Infusions, Parenteral; Injections, Subcutaneous; Pentagastrin; Pepsin A; Perfusion; Secretory Rate; Stomach Ulcer; Thiourea

The new H2-receptor antagonist mifentidine (DA 4577) was tested for its antisecretory and gastric motor effects in comparison with cimetidine and ranitidine. The Shay rat preparation (5 h) was used for studying gastric secretion; the gastric emptying of a liquid meal was chosen for studying gastric motility. All the three compounds inhibited acid secretion in a dose-dependent fashion. Calculated ED50s were 2.3, 12.2 and 92.8 mg X kg-1 for mifentidine, ranitidine and cimetidine, respectively. Therefore, in this animal model, mifentidine was about 40 times more potent than cimetidine and 5 times more potent than ranitidine. As far as gastric emptying is concerned, the effect of equiactive antisecretory doses (i.e. the respective ED50s calculated from the previously established dose-response curves) of all the three antagonists was completely different. Cimetidine delayed emptying rate, whereas ranitidine accelerated it and mifentidine was completely ineffective. However, at higher doses, also this compound affected emptying rate by reducing it dose-dependently. Gastric and duodenal ulcers were induced in the rat by dimaprit (100 mg X kg-1 intravenously) and cysteamine (250 mg X kg-1 subcutaneously), respectively. As far as gastric ulcer is concerned, the ED50s (the effective dose which protected 50% of the animals from lesions) were 0.23, 4.40 and 9.70 mg X kg-1 for mifentidine, ranitidine and cimetidine, respectively. As regards duodenal ulcer, the ED50 was 4.48 for mifentidine and 150.00 mg X kg-1 for ranitidine. In this animal model, the efficacy of cimetidine was very low. Therefore an ED50 could not be determined. In conclusion, results of the present investigation demonstrated that mifentidine is a potent antisecretory compound and an effective anti-ulcer agent in the rat.

Topics: Animals; Bethanechol; Bethanechol Compounds; Cimetidine; Cysteamine; Dimaprit; Duodenal Ulcer; Female; Gastric Juice; Gastrointestinal Motility; Histamine H2 Antagonists; Imidazoles; Male; Ranitidine; Rats; Stomach Ulcer; Thiourea

The protective effect of cimetidine, ranitidine and a newer H2-receptor antagonist, mifentidine (proposed INN), on models of gastric and duodenal damage, caused by activation of H2 receptors, was studied. Gastric erosions were induced in rats by intravenous dimaprit (100 mg/kg) while duodenal damage was investigated in guinea pigs following subcutaneous administration of dimaprit (2 mg/kg, 6 doses). All the compounds reduced or abolished gastric and duodenal damage in rats and guinea pigs, mifentidine being more potent than both cimetidine and ranitidine. The antiulcer effect of the H2-receptor antagonists was related to the dose and to their ability to inhibit dimaprit-induced gastric acid secretion. The duration of action proved to be different for the three compounds. According to the two dosing schedules adopted to evaluate the duration of action, mifentidine, compared to cimetidine and ranitidine, required considerably lower oral dosages to display its protective effect.

Topics: Animals; Cimetidine; Dimaprit; Disease Models, Animal; Duodenal Ulcer; Female; Guinea Pigs; Histamine H2 Antagonists; Imidazoles; Ranitidine; Rats; Rats, Inbred Strains; Receptors, Histamine H2; Stomach Ulcer; Thiourea

Histamine is known to induce gastric ulcers in guinea pigs after intraperitoneal administration and duodenal ulcers after repeated intramuscular administrations. This study was undertaken to clarify further the differential role of H1 and H2 receptor sites in respect to gastric and duodenal ulcer in the guinea pig. Groups of guinea pigs were treated with histamine, intraperitoneal (1.81 mg/kg intraperitoneal) or intramuscular (0.09 mg/kg intramuscular X 8 doses); the selective H2 agonist dimaprit (0.09-0.18 mg/kg X 8 doses intramuscular or 1.81-3.62 mg/kg intraperitoneal); NaCl, 154 mM (control); and the selective H1 and H2 antagonists, diphenhydramine (125 mg/kg X 2 doses, intramuscular) or cimetidine (50 mg/kg X 3 doses, intramuscular). Gastric and duodenal lesions were evaluated and residual gastric contents were analyzed. The selective induction of gastric or duodenal ulceration by histamine was confirmed, and the H2 agonist, dimaprit, has been shown to be ulcerogenic to the guinea pig duodenum by intraperitoneal or intramuscular administration. Diphenhydramine produced considerably more protection against histamine-induced gastric ulceration (62% decrease in incidence), while cimetidine was particularly effective in the prevention of histamine-induced duodenal ulcer (64% decrease in incidence). A differential role of histamine in the pathogenesis of gastric as opposed to duodenal ulcer is suggested by the present findings.

Topics: Animals; Cimetidine; Dimaprit; Diphenhydramine; Duodenal Ulcer; Guinea Pigs; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Injections, Intramuscular; Injections, Intraperitoneal; Male; Receptors, Histamine H1; Receptors, Histamine H2; Stomach Ulcer; Thiourea

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

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

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

Topics: Administration, Oral; Adolescent; Adult; Circadian Rhythm; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Histamine H1 Antagonists; Humans; Hydrogen-Ion Concentration; Imidazoles; Male; Middle Aged; Pain; Parasympatholytics; Placebos; Sensory Receptor Cells; Stomach; Sulfides; Thiourea; Time Factors

Topics: Chemoreceptor Cells; Duodenal Ulcer; Gastric Juice; Histamine H1 Antagonists; Histamine Release; Humans; Imidazoles; Insulin; Sulfides; Thiourea; Vagus Nerve

Topics: Agranulocytosis; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Histamine H1 Antagonists; Humans; Imidazoles; Peptic Ulcer; Receptors, Drug; Sulfides; Thiourea

Metiamide, an antagonist of histamine H(2) receptors, was administered intravenously to normal subjects and to patients with a peptic ulcer during vagal stimulation with a constant infusion of insulin. In normal and peptic-ulcer subjects there were reductions of 70% and 71% respectively in gastric-acid output compared with control tests on the same subjects. The decreased acid output resulted from a reduction in both volume of secretion and acid concentration. Metiamide is therefore a potent inhibitor of vagally-induced gastric acid secretion.

Topics: Adult; Blood Glucose; Depression, Chemical; Duodenal Ulcer; Female; Gastric Juice; Histamine H1 Antagonists; Humans; Imidazoles; Male; Middle Aged; Receptors, Drug; Secretory Rate; Stomach Ulcer; Sulfides; Thiourea; Vagus Nerve

Topics: Adult; Depression, Chemical; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Histamine; Humans; Imidazoles; Infusions, Parenteral; Insulin; Intubation, Gastrointestinal; Pentagastrin; Pepsin A; Peptones; Secretory Rate; Sulfides; Thiourea