H2 receptor antagonist
The PPI omeprazole was found to be more effective at both healing and alleviating symptoms of ulcers and reflux oesophagitis than the H2 blockers ranitidine and cimetidine.
[3] The prototypical H2 antagonist, called cimetidine, was developed by Sir James Black[4] at Smith, Kline & French – now GlaxoSmithKline – in the mid-to-late 1960s.
The use of quantitative structure-activity relationships (QSAR) led to the development of other agents – starting with ranitidine, first sold as Zantac, which was thought to have a better adverse effect profile (later disproven), fewer drug interactions and be more potent.
Cimetidine was the culmination of a project at Smith, Kline & French (SK&F; now GlaxoSmithKline) by James W. Black, C. Robin Ganellin, and others to develop a histamine receptor antagonist that would suppress stomach acid secretion.
It was proposed that the toxicity arose from the thiourea group, and similar guanidine analogues were investigated until the discovery of cimetidine, which would become the first clinically successful H2 antagonist.
Ranitidine (common brand name Zantac) was developed by Glaxo (also now GlaxoSmithKline), in an effort to match the success of Smith, Kline & French with cimetidine.
Ranitidine was also the result of a rational drug design process utilising the by-then-fairly-refined model of the histamine H2 receptor and quantitative structure-activity relationships (QSAR).
The H2 receptor antagonists have since largely been superseded by the even more effective proton pump inhibitors (PPIs), with omeprazole becoming the biggest-selling drug for many years.
There is limited research that histamine H2 receptor antagonists can potentially alleviate symptoms of cystitis[15][16] or painful bladder disease.
[17][18][19] With regard to pharmacokinetics, cimetidine in particular interferes with some of the body's mechanisms of drug metabolism and elimination through the liver cytochrome P450 (CYP) pathway.
Ranitidine is not as potent a CYP inhibitor as cimetidine, although it still shares several of the latter's interactions (such as with warfarin, theophylline, phenytoin, metoprolol, and midazolam).
