metiamide and Peptic-Ulcer

The uses of the histamine H2 receptor antagonists (H2 antagonists) in the management of peptic ulcer disease and the Zollinger-Ellison syndrome are reviewed. Drugs included in the discussion are burimamide, metiamide and cimetidine. The secretion and the pharmacology of the H2 antagonists are described. A discussion of the clinical use of the H2 receptor antagonists in the treatment of gastric hyperacidity and hypersecretory states, and the side effects encountered is presented. Cimetidine is effective in the treatment of duodenal ulcer, and its use appears promising in Zollinger-Ellison syndrome and gastric ulceration.

Topics: Cimetidine; Gastric Juice; Histamine H2 Antagonists; Humans; Metiamide; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Burimamide; Cimetidine; Dogs; Drug Evaluation; Gastric Juice; Histamine; Histamine H2 Antagonists; Humans; Metiamide; Peptic Ulcer; Pyrrolidines; Thiophenes

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

Topics: Anabolic Agents; Humans; Metiamide; Parasympatholytics; Peptic Ulcer; Time Factors

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

Topics: Animals; Burimamide; Cyclic AMP; Gastric Juice; Gastric Mucosa; Guanidines; Heart; Histamine; Histamine H1 Antagonists; Histamine N-Methyltransferase; Histidine Decarboxylase; Humans; Metiamide; Peptic Ulcer; Receptors, Adrenergic; Receptors, Drug

Several new compounds have become available recently which are potent inhibitors of gastric secretion. The therapeutic potential of these inhibitors in the peptic ulcer diathesis is reviewed and it is concluded that the histamine H2-receptor antagonists show most promise at present. The prostaglandins and gastro-intestinal polypeptides are of considerable physiological interest but are unlikely to have clinical importance in the immediate future.

Topics: Animals; Epidermal Growth Factor; Gastric Juice; Gastric Mucosa; Gastrointestinal Hormones; Guanidines; Histamine H2 Antagonists; Humans; Imidazoles; Metiamide; Peptic Ulcer; Prostaglandin Antagonists; Prostaglandins A; Prostaglandins E; Secretin; Somatostatin; Zollinger-Ellison Syndrome

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

Topics: Clinical Trials as Topic; Humans; Metiamide; Palliative Care; Peptic Ulcer; Placebos; Thiourea; Wound Healing

Topics: Animals; Atropine; Benzamides; Clinical Trials as Topic; Depression, Chemical; Gastric Juice; Glutamine; Guinea Pigs; Histamine Antagonists; Humans; Metiamide; Pentagastrin; Peptic Ulcer; Proglumide; Rats; Secretory Rate; Tryptophan

There was still controversy regarding the physiology of acid secretion in 1964 when a team at Smith Kline & French Laboratories in England started a project to prove the existence of more than one receptor for histamine and to find a substance capable of blocking the effects not blocked by the commonly used antihistamines. The team was convinced that histamine was the final mediator of acid secretion. After 8 years, James Black and his coworkers published evidence of the first histamine2-receptor antagonist, burimamide. As this substance was not suitable for oral therapy, the research continued. Metiamide was synthesized with promising clinical effects but questionable safety. The final answer was cimetidine (Tagamet), approved in England in November 1976. Cimetidine was a breakthrough in the treatment of peptic ulcers. In this article I focus on the human factors lying behind many of the decisions made during the years of research. Without personal courage under stressful conditions, the H2-receptor antagonists might never have reached the market.

Topics: Adult; Animals; Burimamide; Cimetidine; Dogs; Drug Industry; England; Histamine H2 Antagonists; History, 20th Century; Humans; Male; Metiamide; Peptic Ulcer; Research; United States

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

Histamine H2-receptor antagonists metiamide and cimetidine were used in the treatment of severe peptic ulceration in Zollinger-Ellison syndrome. The ulcerations were completely healed in all four patients after treatment lasting from six weeks to four-and-a-half-months. Two patients developed recurrent ulcer after the treatment had stopped, but responded to a second course. One patient developed hepatitis B during cimetidine treatment and it is possible that the course of the hepatitis was unfavourable affected by cimetidine. But no other side effects were noted nor was there a significant change in basal serum-gastrin concentration or an increase in H+ secretion. Total gastrectomy remains the treatment of choice in Zollinger-Ellison syndrome, but cimetidine should be considered if the patient refuses operation or operation is not feasible because of a poor general state.

Topics: Adult; Cimetidine; Female; Gastrins; Hepatitis B; Histamine H2 Antagonists; Humans; Male; Metiamide; Peptic Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Animals; Gastric Juice; Male; Metiamide; Peptic Ulcer; Rats; Secretory Rate; Thiourea

Histamine H2-receptor antagonists, including burimamide, metiamide and cimetidine, are effective antagonists of histamine-stimulated acid secretion from mammalian, avian or reptilian gastric mucosa. Acid secretion stimulated by gastrin or pentagastrin is also inhibited by these drugs, but there is disagreement about the effects of these drugs on acid secretion resulting from activation of acetylcholine receptors. Based on the pharmacological evidence possibilities of treatment by these drugs were discussed in cases with excessive stimulation of acid secretion due to high blood levels of histamine or gastrin. The positive results in several trials on Zollinger-Ellison syndrome and peptic ulcer were very impressive. Some practical problems have still to be solved, for example the appropriate phase for applying the drugs. The demonstrated clinical effectiveness, however, against peptic ulceration offers a clear alternative to surgery for many patients.

Topics: Burimamide; Gastric Juice; Gastrins; Guanidines; Histamine H2 Antagonists; Humans; Imidazoles; Metiamide; Parasympatholytics; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Burimamide; Cats; Humans; Metiamide; Peptic Ulcer

Topics: Adult; Female; Guanidines; Humans; Imidazoles; Male; Metiamide; Peptic Ulcer; Zollinger-Ellison Syndrome

In normal and stressed rats with chronic gastric fistula small doses of metiamide (0.001-0.01 muM/kg) increased and doses of over 20 muM/kg decreased gastric acid secretion. In both these dose ranges of dosage metiamide suppressed the development of stress ulcers, most markedly in doses of 0.005 and 100 muM/kg. Intermediate doses had no such action. Only the anti-ulcer action of large doses of metiamide ran parallel to a reduction in acid secretion. Small doses of metiamide increased gastric secretion, but like larger doses, had a weak adrenergic action.

Topics: Animals; Biogenic Amines; Blood Glucose; Brain; Female; Gastric Juice; Gastric Mucosa; Male; Metiamide; Peptic Ulcer; Rats; Receptors, Drug; Stress, Physiological; Thiourea

The new histamine H2-receptor antagonist, metiamide, was shown to inhibit acid and pepsin secretion in gastric secretion studies performed on patients suffering from peptic ulceration. The new drug was administered intravenously in these experiments, but effective plasma levels could also be produced by oral administration. When symptomatic patients were treated with the drug nearly all experienced marked symptomatic relief, and there was some evidence that ulcer healing occurred during treatment. When the drug was withdrawn symptoms tended to return. No toxic reactions were encountered in this trial. Double-blind studies are now being made in Britain to establish the place metiamide may have in the treatment of duodenal ulceration.

Topics: Depression, Chemical; Female; Gastric Juice; Humans; Male; Metiamide; Peptic Ulcer; Thiourea