Omeprazole Prilosec

Structural Formula

Ball-and-Stick Model

Ball-and-Stick Model

Hydrogen A = Oxygen A = Nitrogen = Sulfur

= Carbon

Hydrogen A = Oxygen A = Nitrogen = Sulfur

Year of discovery: late 1970s; Year of introduction: 1987 (Astra Pharmaceuticals, now AstraZeneca) Drug category. Proton pump inhibitor; Main uses: For the treatment of dyspepsia, peptic ulcer disease, and gastroesophageal reflux disease. In combination with antibiotics such as clarithromycin and amoxicillin it is used to eradicate the bacterium Helicobacter pylori that can lead to gastric ulcers; Related drugs: Lansoprazole (Prevacid), Rabeprazole (Aciphex), Pantoprazole (Protonix).

During the late 1970s researchers at Astra Pharmaceuticals in Sweden (now AstraZeneca) developed omeprazole (Prilosecâ„¢), the first gastric proton pump inhibitor. Proton pump inhibitors irreversibly block the hydrogen/potassium adenosine triphosphate enzyme system (H+/K+ ATPase) that is responsible for the secretion of acid into the stomach. Omeprazole allows the reduction of gastric acid secretion to very low levels in a dose-dependent way. A key structural feature of omeprazole (and other proton pump inhibitors) is the presence of a sulfoxide functional group (shown above in green) between the benzimidazole (red) and pyridine (blue) rings.

Omeprazole is administered orally. At neutral pH, it is both stable and devoid of proton pump inhibitory activity. However, it is activated once it reaches the parietal cells of the stomach via the bloodstream. In the acidic environment of the stomach omeprazole undergoes an acid-catalyzed rearrangement (see scheme at right) to form a reactive species (sulfenamide), which attacks and inactivates the enzyme H+/K+ ATPase.1 As a result, the proton pump is shut off and gastric acidity is lowered.

Due to the overall lipophilicity of omeprazole, it readily crosses cell membranes and has high bioavailability. In terms of both potency and bioavailability, proton pump inhibitors have proved superior to H2-receptor antagonists in the reduction of gastric acidity.2,3

Annual sales of omeprazole approached $7 billion in 2001.

Omeprazole

N L Rearrangement n h oh ch3 ^v och3 Sulfenic Acid

Omeprazole och3 Sulfenic Acid

Loss of water (H20)

ochj

Inactive Enzyme-Omeprazole Complex hs -q (Enzyme)

ochj

Inactive Enzyme-Omeprazole Complex ochj

Sulfenamide ochj

Sulfenamide

Omeprazole is a mixture of enantiomers. The (S)-enantiomer, the active form, is now available as a proprietary product under the brand name Nexiumâ„¢.

1. Trends Pharmacol. Sci. 1987, 8, 399-402; 2. Therapy 2006, 3. 227-236; 3. Aliment. Pharmacol. Ther. 2006, 24. 743-750; Refs. p. 107

0 0

Post a comment