GASTRIC SECRETION INHIBITORS act at some stage in the control process to inhibit the enzymic or gastric acid secretions of the stomach, with the latter being a major therapeutic target. The neuronal, hormonal and paracrine control of gastric acid secretion from the parietal cells of the gastric mucosa is complex. The pathways involved include acetylcholine via the parasympathetic innervation of the stomach, the hormone gastrin. the paracrine agent histamine and possibly the paracrine hormone gastrin-releasing peptide.
Anticholinergic agents have not proved very valuable in the long-run, having a limited ability to reduce acid secretion at doses that can be tolerated in view of widespread side-effects. Some more recently developed agents show gastric-selectivity (they are Mrcholinoceptor-preferring ligands, which may be the reason for their selectivity), e.g. pirenzepine and telenzepine: see muscarinic cholinoceptor antagonists.
Gastrin receptor antagonists and gastrin-releasing peptide antagonists have now been developed for experimental use, but it is not yet clear if either will be useful clinically. See BOMBESIN RECEPTOR ANTAGONISTS; CHOLECYSTOKININ RECEPTOR ANTAGONISTS.
Histamine H2-receptor antagonists are very effective in reducing acid secretion and have considerable usage, e.g. cimetidine, famotidine. nizatidine and ranitidine. These agents are used to treat gastric and duodenal ulcer, dyspepsia, reflux oesophagi tis, Zollinger-Ellison syndrome and a number of related disorders. They are relatively safe and free of side-effects. See histamine h2-receptor antagonists.
Gastric proton pump inhibitors act to reduce gastric acid secretion in the stomach, by irreversibly blocking the H*/K*-ATPase, and markedly reduce both basal and stimulated gastric acid secretion. Examples of those so far in use are lansoprazole, omeprazole, pantoprazole and rabeprazole, and they react with sulphydryl groups of the proton pump. This type of drug is valuable in the treatment of peptic ulcers resistant to histamine H2 antagonists, for reflux oesophagitis and are the drugs of choice for Zollinger-Ellison syndrome. They may also be used concurrently with antimicrobial agents to eliminate Helicobacter pylori infection, a bacterium peculiar to the environment of the stomach and thought to be involved with the aetiology of peptic ulcers (and possibly carcinoma of the stomach). See GASTRIC PROTON PUMP inhibitors.
Other agents that are effective in healing peptic ulceration probably do not work through inhibiting gastric acid secretion, but have some other form of protective action. These other agents include prostaglandin analogues (e.g. misoprostol: see prostanoid receptor agonists), bismuth chelates (e.g. tripotassium dicitratobismuthate), complexes: (e.g. sucralfate) and liquorice derivatives (e.g. carbenoxolone).