| InChI | InChI=1S/C19H24N2O4S2/c22-17(15(26)11-12-5-2-1-3-6-12)20-13-9-10-27-16-8-4-7-14(19(24)25)21(16)18(13)23/h1-3,5-6,13-16,26H,4,7-11H2,(H,20,22)(H,24,25)/t13-,14-,15-,16-/m0/s1 |
| Reference | 1. Curr Hypertens Rep. 2001 Dec;3 Suppl 2:S22-7.
<br>
Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and
Angiotensin-converting enzyme activity in humans.
<br>
Vesterqvist O(1), Reeves RA.
<br>
Author information: <br>
(1)Clinical Laboratory, Pharmaceutical Research Institute, Bristol-Myers Squibb,
Three Hamilton Health Place, Hamilton, NJ 08690, USA. [email protected]
<br>
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.
<br>
2. Heart Dis. 2000 May-Jun;2(3):266-74.
<br>
Omapatrilat: a unique new agent for the treatment of cardiovascular disease.
<br>
Nawarskas JJ(1), Anderson JR.
<br>
Author information: <br>
(1)University of New Mexico College of Pharmacy, 2502 Marble Northeast,
Albuquerque, NM 87131-5691, USA. [email protected]
<br>
Omapatrilat is the most clinically advanced of a new class of drugs,
vasopeptidase inhibitors, which are being studied for the treatment of patients
with cardiovascular disease. Omapatrilat inhibits the enzymatic activities of
angiotensin-converting enzyme and neutral endopeptidase. The end result is
blockade of angiotensin-II formation and inhibition of the catabolism of
vasodilatory hormones, such as the natriuretic peptides, bradykinin, and
adrenomedullin. Some of the ultimate pharmacologic effects include vasodilation,
natriuresis, and diuresis, which may be beneficial in the management of various
cardiovascular diseases, such as hypertension and heart failure. The
pharmacokinetics of omapatrilat are compatible with once-daily dosing and a
duration of antihypertensive efficacy of more than 24 hours. Omapatrilat
decreases blood pressure in both high-renin and low-renin states, which suggests
antihypertensive efficacy that is independent of the status of the
renin-angiotensin system. Furthermore, the antihypertensive effect of omapatrilat
is indiscriminate of age or race. Omapatrilat has consistently shown efficacy in
decreasing both systolic and diastolic blood pressure to a similar or greater
extent than either lisinopril or amlodipine; however, systolic pressure is more
responsive to omapatrilat treatment than diastolic pressure. Although the role of
omapatrilat in heart failure is still evolving, preliminary results are
promising: hemodynamic improvements and clinical benefits of omapatrilat are
similar or greater to those achieved with an angiotensin-converting enzyme
inhibitor. Future studies (specifically the OVERTURE Study) will be of pivotal
importance in establishing the role of omapatrilat in the treatment of patients
with heart failure. The side-effect and drug-interaction profiles of omapatrilat
are largely incomplete, but suggest excellent tolerability and a side-effect
profile that is similar to placebo. Omapatrilat could be a revolutionary addition
to the management of cardiovascular disease, and its clinical development will be
followed closely by many who are curious if larger clinical trials will echo the
impressive preliminary data that have been seen thus far.
<br>
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