The pharmacology of histamine H2-receptor antagonists

The structure of the first histamine H2-receptor antagonist, burimamide was described in 1972. Since then, numerous compounds with diverse chemical structures have been shown to possess H2-receptor antagonist activity. Most of these compounds comprise an aromatic ring and polar group linked by a flexible chemical chain. Currently five H2-receptor antagonists are available for therapeutic use. In vitro studies have confirmed the competitive nature of the interaction between agonist and antagonist for these compounds and a comparison of the pA2 values generated shows a rank order of potency cimetidine less than nizatidine = ranitidine less than or equal to roxatidine less than famotidine. The duration of action of these agents is largely dependent upon their pharmacokinetic properties; with the possible exception of roxatidine, all have plasma elimination half-lives in the range 2-4 hours. Competitive antagonists with a high degree of selectivity for the H2-receptor and with a longer duration of action are currently being investigated, e.g., sufotidine. In addition to competitive agents, several non-competitive H2-antagonists, e.g., loxtidine, have been described. These have a prolonged duration of action. Relative potency varies between animal species and pharmacological models studied but the results of animal pharmacological studies have generally provided a good indication of the likely effects in man. Studies of 24-hour intragastric acidity represent the most physiological model available in man for evaluating the effects of different antisecretory drug regimens. Comparative studies with ranitidine 150 mg b.i.d. and cimetidine 400 mg b.i.d. have shown a reduction in 24-hour acidity of 65% and 30%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)