Soraprazan: Setting New Standards in Inhibition of Gastric Acid Secretion.
From: Department of Biochemistry Gastroenterology, ALTANA Pharma AG, Byk-Gulden Strasse 2, 78467 Konstanz, Germany.
The Journal of pharmacology and experimental therapeutics
- Publish Date: Jun 2007
- ISSN: 0022-3565
- Volume: 321
- Issue: 3
- Pages: 866-74
- Medium: Print
- Language: English
- Citation (JAMA): Simon W A, Herrmann M, Klein T, et al. Soraprazan: Setting New Standards in Inhibition of Gastric Acid Secretion.. J. Pharmacol. Exp. Ther. Jun 2007;321:866-74
Abstract
After treatment of millions of patients suffering from gastroesophageal reflux disease (GERD) and other acid-related ailments with proton pump inhibitors, there are still unmet medical needs such as rapid and reliable pain relief, especially for nocturnal acid breakthrough. In this work, we introduce and characterize the biochemistry and pharmacology of the potassium-competitive acid blocker (P-CAB) soraprazan, a novel, reversible, and fast-acting inhibitor of gastric H,K-ATPase. Inhibitory and binding properties of soraprazan were analyzed together with its mode of action, its selectivity, and its in vivo potency. This P-CAB has an IC(50) of 0.1 microM if measured with ion leaky vesicles and of 0.19 microM in isolated gastric glands. With a K(i) of 6.4 nM, a K(d) of 26.4 nM, and a B(max) of 2.89 nmol/mg, this compound is a highly potent and reversible inhibitor of the H,K-ATPase. Soraprazan shows immediate inhibition of acid secretion in various in vitro models and in vivo and was found to be more than 2000-fold selective for H,K-ATPase over Na,K- and Ca-ATPases. Soraprazan is superior to esomeprazole in terms of onset of action and the extent and duration of pH elevation in vivo in the dog. Rapid and consistent inhibition of acid secretion by soraprazan renders the P-CABs a promising group of compounds for therapy of GERD.
Mesh Headings (Keywords): Animals, Anti-Ulcer Agents, Benzazepines, Dogs, Enzyme Inhibitors, Gastric Acid, Gastric Mucosa, Gene Expression, H(+)-K(+)-Exchanging ATPase, Humans, Hydrogen-Ion Concentration, Imidazoles, Kinetics, Male, Molecular Structure, Naphthyridines, Niacinamide, Nigericin, Omeprazole, Potassium, Rabbits, Sodium-Potassium-Exchanging ATPase, Stomach, Swine
Check for Full Text / PubMed Unique Identifier (PMID): 17369284
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.