H2 receptor antagonist

H₂ antagonists, sometimes referred to as H2RAs^[1] and also called H₂ blockers, are a class of medications that block the action of histamine at the histamine H₂ receptors of the parietal cells in the stomach. This decreases the production of stomach acid. H₂ antagonists can be used in the treatment of dyspepsia, peptic ulcers and gastroesophageal reflux disease. They have been surpassed by proton pump inhibitors (PPIs). 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.^[2]

H₂ antagonists, which all end in "-tidine", are a type of antihistamine. In general usage, however, the term "antihistamine" typically refers to H₁ antagonists, which relieve allergic reactions. Like the H₁ antagonists, some H₂ antagonists function as inverse agonists rather than receptor antagonists, due to the constitutive activity of these receptors.^[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. It was first marketed in 1976 and sold under the trade name Tagamet, which became the first blockbuster drug. 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.