What is the mechanism of action of vasopeptidase inhibitors?

Drugs of this class have a dual mechanism of action: they simultaneously block the angiotensin-converting enzyme (reducing renin-angiotensin system activity) and neutral endopeptidase (preventing the degradation of endogenous vasodilating peptides).

Why is omapatrilat not used in modern clinical practice?

Despite its high efficacy and prolonged duration of action, the drug did not find clinical application due to frequent and severe adverse reactions, specifically the development of angioedema.

What are the main pharmacokinetic parameters of omapatrilat?

The drug is well absorbed (30% bioavailability), reaches peak concentration in 2 hours, has a half-life of 14–19 hours (action lasts over 24 hours), and is excreted by the kidneys as metabolites.

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Vasopeptidase Inhibitors

*Omapatrilatum*

For medical students2 min readUpdated 2026-10-10

Vasopeptidase inhibitors are a class of pharmacological agents with a dual mechanism of action. A prominent representative of this group is omapatrilat, which simultaneously blocks the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP).

DrugOmapatrilat (representative of a novel class)

MechanismDual blockade: ACE and neutral endopeptidase

Half-lifet1/2 is 14–19 hours, duration of action > 24 hours

Clinical statusNot introduced into practice due to angioedema

Dual Mechanism of Action

The distinct feature of vasopeptidase inhibitors is their simultaneous action on two key targets in the body:

ACE blockade — inhibits the activity of the renin-angiotensin system, which eliminates the vasopressor effect.
Neutral endopeptidase blockade — this enzyme normally degrades endogenous vasodilating peptides. Suppressing its activity enhances the effects of vasodilatory systems.

As a result of this combined effect, blood pressure decreases due to the simultaneous suppression of vasoconstriction and enhancement of vasodilation.

Pharmacokinetic Features

This class representative is characterized by the following parameters:

Well absorbed with a bioavailability of about 30%.
Peak blood concentration is reached 2 hours after administration.
The half-life ($t_{1/2}$) ranges from 14–19 hours, providing a duration of action of more than 24 hours.
Metabolites are excreted by the kidneys.

Clinical Status and Reasons for Discontinuation

Despite its high efficacy in lowering blood pressure through dual blockade, the drug has not entered routine clinical practice. The main reason for discontinuing its use was the high incidence of a severe adverse effect — angioedema.

Mnemonic

Omapatrilat: A double hit on blood pressure (ACE + neutral endopeptidase), but dangerous angioedema blocks its path to the clinic.

Frequently asked questions

What is the mechanism of action of vasopeptidase inhibitors?: Drugs of this class have a dual mechanism of action: they simultaneously block the angiotensin-converting enzyme (reducing renin-angiotensin system activity) and neutral endopeptidase (preventing the degradation of endogenous vasodilating peptides).
Why is omapatrilat not used in modern clinical practice?: Despite its high efficacy and prolonged duration of action, the drug did not find clinical application due to frequent and severe adverse reactions, specifically the development of angioedema.
What are the main pharmacokinetic parameters of omapatrilat?: The drug is well absorbed (30% bioavailability), reaches peak concentration in 2 hours, has a half-life of 14–19 hours (action lasts over 24 hours), and is excreted by the kidneys as metabolites.

Go deeper

The role of neutral endopeptidase in vascular tone regulation
Interaction between the renin-angiotensin system and vasodilating peptides
Pharmacokinetics of omapatrilat: absorption, peak concentration, and renal clearance
Pathogenesis of angioedema in vasopeptidase blockade
Prospects for molecular modification to create safe vasopeptidase blockers