| Drug ID: | D259 |
| Drug Name: | Omeprazole |
| Synonyms: |
OMEP; Omeprazole
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| Type: | Chemical drug |
| DrugBank ID: |
DB00338
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| DrugBank Description: |
Originally approved by the FDA in 1989, omeprazole is a _proton-pump inhibitor_, used to treat gastric acid-related disorders. These disorders may include gastroesophageal reflux disease (GERD), peptic ulcer disease, and other diseases characterized by the oversecretion of gastric acid. This drug was the first clinical useful drug in its class, and its approval was followed by the formulation of many other proton pump inhibitor drugs . Omeprazole is generally effective and well-tolerated, promoting its popular use in children and adults .
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| PubChem ID: |
4594
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| CasNo: |
73590-58-6
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| Repositioning for NAFLD: |
Yes
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| SMILES: |
S(=O)(Cc1c(C)c(OC)c(cn1)C)c1nc2c([nH]1)ccc(c2)OC
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| Structure: |
|
| InChiKey: |
SUBDBMMJDZJVOS-UHFFFAOYSA-N
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| Molecular Weight: |
345.424
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| DrugBank Targets: |
Potassium-transporting ATPase alpha chain 1 inhibitor; Aryl hydrocarbon receptor agonist
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| DrugBank MoA: |
Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump , expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid) .
Omeprazole is a member of a class of antisecretory compounds, the substituted _benzimidazoles_, that stop gastric acid secretion by selective inhibition of the _H+/K+ ATPase_ enzyme system. Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of the _H+/K+ ATPase_ pump, inhibiting gastric acid secretion for up to 36 hours . This antisecretory effect is dose-related and leads to the inhibition of both basal and stimulated acid secretion, regardless of the stimulus .
**Mechanism of H. pylori eradication**
Peptic ulcer disease (PUD) is frequently associated with _Helicobacter pylori_ bacterial infection (NSAIDs) . The treatment of H. pylori infection may include the addition of omeprazole or other proton pump inhibitors as part of the treatment regimen , .
_H. pylori_ replicates most effectively at a neutral pH . Acid inhibition in H. pylori eradication therapy, including proton-pump inhibitors such as omeprazole, raises gastric pH, discouraging the growth of H.pylori . It is generally believed that proton pump inhibitors inhibit the _urease_ enzyme, which increases the pathogenesis of H. pylori in gastric-acid related conditions .
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| DrugBank Pharmacology: |
**Effects on gastric acid secretion**
This drug decreases gastric acid secretion . After oral administration, the onset of the antisecretory effect of omeprazole is usually achieved within one hour, with the maximum effect occurring by 2 hours after administration. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days .
**Effects on serum gastrin**
In studies of 200 or more patients, serum gastrin levels increased during the first 1-2 weeks of daily administration of therapeutic doses of omeprazole. This occurred in a parallel fashion with the inhibition of acid secretion. No further increase in serum gastrin occurred with continued omeprazole administration. Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A (CgA) levels. The increased CgA levels may lead to false positive results in diagnostic studies for neuroendocrine tumors .
**Enterochromaffin-like (ECL) cell effects**
Human gastric biopsy samples have been obtained from more than 3000 pediatric and adult patients treated with omeprazole in long-term clinical studies. The incidence of enterochromaffin-like cell hyperplasia in these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia have been identified in these patients. These studies, however, are of insufficient in power and duration to draw conclusions on the possible influence of long-term administration of omeprazole in the development of any premalignant or malignant conditions .
**Other effects**
Systemic effects of omeprazole in the central nervous system, cardiovascular and respiratory systems have not been found to date. Omeprazole, given in oral doses of 30 or 40 mg for 2-4 weeks, showed no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretin .
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| DrugBank Indication: |
Omeprazole, according to the FDA label is a proton pump inhibitor (PPI) used for the following purposes:
• Treatment of active duodenal ulcer in adults
• Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer
recurrence in adults
• Treatment of active benign gastric ulcer in adults
• Treatment of symptomatic gastroesophageal reflux disease (GERD) in
patients 1 year of age and older
• Treatment of erosive esophagitis (EE) due to acid-mediated GERD in
patients 1 month of age and older
• Maintenance of healing of EE due to acid-mediated GERD in patients 1
year of age and older
• Pathologic hypersecretory conditions in adults
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| Targets: |
AHR agonist
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| Therapeutic Category: |
--
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| Clinical Trial Progress: |
Phase 2 completed (NCT01876108)
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| Latest Progress: |
Under clinical trials
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