Control of gastric acid secretion by histamine H2 receptor antagonists and anticholinergics

The control of gastric secretion may be obtained by means of several pharmacological compounds: histamine H2 receptor antagonists and anticholinergics are so far the most widely employed drugs in pharmacological experiments and in clinical practice. The H2 blockers are able to inhibit the secretory response to histamine, acetylcholine and gastrin; they are effective and safe and at present they have been employed in several million patients suffering from diseases characterized by acid hyperproduction. The compounds available on the market are cimetidine, ranitidine, famotidine and nizatidine; however, approximately 11,000 compounds of the family have been synthesized and about 20 of these are under clinical evaluation. The blockade of H2 receptors is the primary action of these drugs; however, they possess also secondary actions which may represent untoward effects but in some cases may be actually useful (increase in prostaglandin synthesis, inhibition of LTB4 synthesis, etc.) The 'classic' anticholinergics appear to be decidedly less important mainly from a therapeutic point of view. However, the new compounds like pirenzepine and telenzepine, which block specifically the so-called M1 receptors located in the ganglia of the myenteric plexus, may represent an alternative to the H2 blockers since they are virtually devoid of the untoward reactions typical for the old atropine-like compounds (dry mouth, mydriasis, tachycardia, etc.) Both H2 blockers and the new antimuscarinic compounds may have effects not only on the parietal cells but also on other sites (G-cells, histaminocytes, D-cells) which control the function of the parietal cells themselves.