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CC BY-NC-ND 4.0 · Avicenna J Med 2021; 11(01): 1-7
DOI: 10.4103/ajm.ajm_117_20
Review Article

Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials

Sara Abdulrahman Alomar
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
,
Sarah Ali Alghabban
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
,
Hadeel Abdulaziz Alharbi
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
,
Mehad Fahad Almoqati
College of Medicine, Taif University, Taif, Saudi Arabia
,
Yazid Alduraibi
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
,
Ahmed Abu-Zaid
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, United States
› Author Affiliations
Subject Editor: Financial support and sponsorship Nil.
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Abstract

An unfortunate subset of hypertensive patients develops resistant hypertension in which optimal doses of three or more first-line antihypertensive drugs fail to sufficiently control blood pressure. Patients with resistant hypertension represent a high-risk and difficult-to-treat group, and such patients are at amplified jeopardies for substantial hypertension-related multi-organ failure, morbidity, and mortality. Thus, there is a pressing requirement to better improve blood pressure control through the pharmaceutical generation of novel classes of antihypertensive drugs that act on newer and alternative therapeutic targets. The hyperactivity of the brain renin-angiotensin system (RAS) has been shown to play a role in the pathogenesis of hypertension in various experimental and genetic hypertensive animal models. In the brain, angiotensin-II is metabolized to angiotensin-III by aminopeptidase A (APA), a membrane-bound zinc metalloprotease enzyme. A large body of evidence has previously established that angiotensin-III is one of the main effector peptides of the brain RAS. Angiotensin-III exerts central stimulatory regulation over blood pressure through several proposed mechanisms. Accumulating evidence from preclinical studies demonstrated that the centrally acting APA inhibitor prodrugs (firibastat and NI956) are very safe and effective at reducing blood pressure in various hypertensive animal models. The primary purpose of this study is to narratively review the published phase I–II literature on the safety and efficacy of APA inhibitors in the management of patients with hypertension. Moreover, a summary of ongoing clinical trials and future perspectives are presented.

Keywords

Angiotensin III - blood pressure - brain aminopeptidase a - brain renin-angiotensin system - firibastat - hypertension


Publication History

Article published online:
06 August 2021

© 2021. Syrian American Medical Society. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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