Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and Angiotensin-converting enzyme activity in humans.
Vasopeptidase inhibition is a new concept in blood pressure management. A single molecule simultaneously inhibits two enzymes that regulate cardiovascular function: neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE)[1]. Development of vasopeptidase inhibitors stemmed from the need for new and more efficacious antihypertensive agents that not only reduce blood pressure but also treat hypertension as part of a larger syndrome involving endothelial dysfunction [2]. By inhibiting NEP and ACE, vasopeptidase inhibitors enhance the natriuretic peptide and kallikrein-kinin systems and inhibit the renin-angiotensin-aldosterone system. This article outlines the pharmacodynamic effects of the vasopeptidase inhibitor omapatrilat on biomarkers of NEP and ACE activity in humans.
Vesterqvist
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Clinical Laboratory, Pharmaceutical Research Institute, Bristol-Myers Squibb, Three Hamilton Health Place, Hamilton, NJ 08690, USA. ole.vesterqvist@bms.com
Reeves
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RA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013841:Thiazepines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D011725:Pyridines; D013841:Thiazepines; D014665:Vasodilator Agents; C106266:omapatrilat; D009320:Atrial Natriuretic Factor; D015260:Neprilysin