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

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 pati...

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Autores principales:	Sara Abdulrahman Alomar, Sarah Ali Alghabban, Hadeel Abdulaziz Alharbi, Mehad Fahad Almoqati, Yazid Alduraibi, Ahmed Abu-Zaid
Formato:	article
Lenguaje:	EN
Publicado:	Thieme Medical and Scientific Publishers Pvt. Ltd. 2021
Materias:	angiotensin iii blood pressure brain aminopeptidase a brain renin-angiotensin system firibastat hypertension Medicine R
Acceso en línea:	https://doaj.org/article/5afe9e6fa7fa466cbd872672f3cc700a
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spelling	oai:doaj.org-article:5afe9e6fa7fa466cbd872672f3cc700a2021-12-02T19:02:51ZFiribastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials2231-07702249-446410.4103/ajm.ajm_117_20https://doaj.org/article/5afe9e6fa7fa466cbd872672f3cc700a2021-01-01T00:00:00Zhttp://www.thieme-connect.de/DOI/DOI?10.4103/ajm.ajm_117_20https://doaj.org/toc/2231-0770https://doaj.org/toc/2249-4464An 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.Sara Abdulrahman AlomarSarah Ali AlghabbanHadeel Abdulaziz AlharbiMehad Fahad AlmoqatiYazid AlduraibiAhmed Abu-ZaidThieme Medical and Scientific Publishers Pvt. Ltd.articleangiotensin iiiblood pressurebrain aminopeptidase abrain renin-angiotensin systemfiribastathypertensionMedicineRENAvicenna Journal of Medicine, Vol 11, Iss 01, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	angiotensin iii blood pressure brain aminopeptidase a brain renin-angiotensin system firibastat hypertension Medicine R
spellingShingle	angiotensin iii blood pressure brain aminopeptidase a brain renin-angiotensin system firibastat hypertension Medicine R Sara Abdulrahman Alomar Sarah Ali Alghabban Hadeel Abdulaziz Alharbi Mehad Fahad Almoqati Yazid Alduraibi Ahmed Abu-Zaid Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials
description	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.
format	article
author	Sara Abdulrahman Alomar Sarah Ali Alghabban Hadeel Abdulaziz Alharbi Mehad Fahad Almoqati Yazid Alduraibi Ahmed Abu-Zaid
author_facet	Sara Abdulrahman Alomar Sarah Ali Alghabban Hadeel Abdulaziz Alharbi Mehad Fahad Almoqati Yazid Alduraibi Ahmed Abu-Zaid
author_sort	Sara Abdulrahman Alomar
title	Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials
title_short	Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials
title_full	Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials
title_fullStr	Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials
title_full_unstemmed	Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials
title_sort	firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials
publisher	Thieme Medical and Scientific Publishers Pvt. Ltd.
publishDate	2021
url	https://doaj.org/article/5afe9e6fa7fa466cbd872672f3cc700a
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Firibastat, the first-in-class brain aminopeptidase a inhibitor, in the management of hypertension: a review of clinical trials

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