burimamide and Peptic-Ulcer

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: 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

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

For the definition of histamine receptors the following prerequisites must be fulfilled: (1) Course of dose-response curves according to the mass-action law; (2) parallel displacement of these curves to the right in the presence of antagonists; (3) inhibition only by specific histamine antagonists; (4) slope of a Schild-plot not significantly different from unity. For H2-receptors these prerequisites could ideally be fulfilled, especially by the development of highly specific H2-receptor antagonists. However, this new class of compounds acts not only by mere competitive inhibition of histamine at its H2-receptor, but also by activating the metabolism of this secretagogue. A further explanation of the action of H2-receptor antagonists in the treatment of chronic duodenal ulcer may be given by studying the pathogenetic role played by histamine in the development of this disease: duodenal ulcer patients showed an increased liberation of histamine from mucosal mast cell stores as well as a decreased activity of histamine methyltransferase (i. e. longer action of histamine!). The rise in histamine content and histamine methyltransferase activity after vagotomy may be the basis for a biochemical explanation of the acid-reducing effect of this operation.

Topics: Animals; Burimamide; Cats; Cimetidine; Dogs; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Histamine H2 Antagonists; Histamine N-Methyltransferase; Humans; Male; Mast Cells; Pentagastrin; Peptic Ulcer; Rats; Receptors, Histamine H2; Vagotomy

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, 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