| Drug ID: | D213 |
| Drug Name: | Esomeprazole |
| Synonyms: |
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| Type: | small molecule |
| DrugBank ID: |
DB00736
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| DrugBank Description: |
Esomeprazole, sold under the brand name Nexium, is a proton pump inhibitor (PPI) medication used for the management of gastroesophageal reflux disease (GERD), for gastric protection to prevent recurrence of stomach ulcers or gastric damage from chronic use of NSAIDs, and for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome. It can also be found in quadruple regimens for the treatment of _H. pylori_ infections along with other antibiotics including [DB01060], [DB01211], and [DB00916], for example.[A177271, F4498] Its efficacy is considered similar to other medications within the PPI class including [DB00338], [DB00213], [DB00448], [DB05351], and [DB01129]. Esomeprazole is the s-isomer of [DB00338], which is a racemate of the S- and R-enantiomer. Esomeprazole has been shown to inhibit acid secretion to a similar extent as [DB00338], without any significant differences between the two compounds _in vitro_.
Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect persists longer than 24 hours.[FDA Label]
PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes.[A177577, A177580]
Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients such as iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.[A177571]
Rapid discontinuation of PPIs such as esomeprazole may cause a rebound effect and a short term increase in hypersecretion.[A177574] Esomeprazole doses should be slowly lowered, or tapered, before discontinuing to prevent this rebound effect.
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| PubChem ID: |
9568614
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| CasNo: |
119141-88-7
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| Repositioning for NAFLD: |
Yes
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| SMILES: |
COC1=CC2=C(NC(=N2)[S@@](=O)CC2=NC=C(C)C(OC)=C2C)C=C1
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| Structure: |
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| InChiKey: |
SUBDBMMJDZJVOS-DEOSSOPVSA-N
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| Molecular Weight: |
345.416
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| DrugBank Targets: |
Potassium-transporting ATPase alpha chain 1; N(G),N(G)-dimethylarginine dimethylaminohydrolase 1
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| DrugBank MoA: |
Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect that persists longer than 24 hours.[FDA Label]
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| DrugBank Pharmacology: |
Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and <i>H. pylori</i> eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H<sup>+</sup>/K<sup>+</sup> ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
Esomeprazole is the s-isomer of [DB00338], which is a racemate of the S- and R-enantiomer. Esomeprazole has been shown to inhibit acid secretion to a similar extent as [DB00338], without any significant differences between the two compounds _in vitro_.
PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes.[A177577, A177580]
Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.[A177571]
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| DrugBank Indication: |
Esomeprazole is indicated for the treatment of acid-reflux disorders including healing and maintenance of erosive esophagitis, and symptomatic gastroesophageal reflux disease (GERD), peptic ulcer disease, H. pylori eradication, prevention of gastrointestinal bleeds with NSAID use, and for the long-term treatment of pathological hypersecretory conditions including Zollinger-Ellison Syndrome.
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