Omapatrilat
Omapatrilat
Omapatrilat is a pharmaceutical compound that was investigated as a treatment for hypertension and heart failure. It is a member of a class of drugs known as vasopeptidase inhibitors, which act by inhibiting both the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). This dual inhibition was hypothesized to provide superior cardiovascular benefits compared to traditional ACE inhibitors.
Mechanism of Action
Omapatrilat works by simultaneously inhibiting two key enzymes involved in the regulation of blood pressure and fluid balance. The inhibition of angiotensin-converting enzyme leads to decreased production of angiotensin II, a potent vasoconstrictor, thereby reducing blood pressure. Additionally, the inhibition of neutral endopeptidase prevents the breakdown of natriuretic peptides, which promote vasodilation and natriuresis, further contributing to blood pressure reduction.
Clinical Development
Omapatrilat was developed by Bristol-Myers Squibb and underwent extensive clinical trials to evaluate its efficacy and safety. Initial studies showed promising results in lowering blood pressure more effectively than existing treatments. However, during the clinical trials, a significant incidence of angioedema was observed, which raised concerns about the safety of the drug.
Safety Concerns
The occurrence of angioedema, a potentially life-threatening condition characterized by swelling of the deeper layers of the skin, was a major safety concern during the trials of omapatrilat. This adverse effect was attributed to the accumulation of bradykinin, a peptide that is normally degraded by ACE. The dual inhibition of ACE and NEP by omapatrilat led to higher levels of bradykinin, increasing the risk of angioedema.
Discontinuation
Due to the safety concerns, particularly the risk of angioedema, the development of omapatrilat was discontinued. The Food and Drug Administration (FDA) did not approve the drug for clinical use, and it was never marketed.
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