The development of H2-receptor antagonists was based on the observation that H1 antagonists had no effect on histamine-induced acid secretion in the stomach. Molecular manipulation of the histamine molecule resulted in drugs that blocked acid secretion and had no H1 agonist or antagonist effects. Like the other hista-mine receptors, the H2 receptor displays constitutive activity, and some H2 blockers are inverse agonists.
The high prevalence of peptic ulcer disease created great interest in the therapeutic potential of the H2-receptor antagonists when first discovered. Although these agents are not the most efficacious avail-able, their ability to reduce gastric acid secretion with very low toxicity has made them extremely popular as over-the-counter preparations.