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Famotidine, sold under the brand name Pepcid among others, is a histamine H 2 receptor antagonist medication that decreases stomach acid production. [4] It is used to treat peptic ulcer disease , gastroesophageal reflux disease , and Zollinger-Ellison syndrome . [ 4 ]
A derivative of timoprazole, omeprazole, was discovered in 1979, and was the first of a new class of drug that control acid secretion in the stomach, a proton pump inhibitor (PPI). [11] [12] Addition of 5-methoxy-substitution to the benzimidazole moiety of omeprazole was also made and gave the compound much more stability at neutral pH. [6]
Most of these medications are benzimidazole derivatives, related to omeprazole, but imidazopyridine derivatives such as tenatoprazole have also been developed. [77] Potassium-competitive inhibitors such as revaprazan reversibly block the potassium-binding site of the proton pump, acting more quickly, but are not available in most countries.
Cimetidine was the prototypical histamine H 2 receptor antagonist from which later drugs were developed. 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.
Acute use (1–3 days) yields a potency about 1.5× stronger than that of morphine and chronic use (7 days+) yields a potency about 2.5 to 5× that of morphine. Similarly, the effect of tramadol increases after consecutive dosing due to the accumulation of its active metabolite and an increase of the oral bioavailability in chronic use.
Omeprazole was patented in 1978 and approved for medical use in 1988. [15] [16] It is on the World Health Organization's List of Essential Medicines. [17] It is available as a generic medication. [1] In 2022, it was the ninth most commonly prescribed medication in the United States, with more than 52 million prescriptions.
Omeprazole is a popular drug that conforms to Lipinski's rule of five. Some authors have criticized the rule of five for the implicit assumption that passive diffusion is the only important mechanism for the entry of drugs into cells, ignoring the role of transporters. For example, O'Hagan and co-authors wrote as follows: [5]
Gastric adverse effects may be reduced by taking medications that suppress acid production such as proton pump inhibitors (e.g.: omeprazole and esomeprazole), or by treatment with a drug that mimics prostaglandin in order to restore the lining of the GI tract (e.g.: a prostaglandin analog misoprostol). [40]
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