Current Knowledge about the New Drug Firibastat in Arterial Hypertension

Figures

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  Figure 1. Schematic diagram of the brain renin–angiotensin system. Abbreviations: Angiotensin-converting enzyme (ACE), angiotensin-converting enzyme type 2 (ACE2), aminopeptidase A (APA), aminopeptidase N (APN), angiotensin receptor type 1 (AT1), angiotensin receptor type 2 (AT2). Modified for this review from [35].

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  Figure 2. The prodrug RB150 (firibastat) can cross the blood–brain barrier after oral administration because of the disulfide bridge. RB150 consists of 2 EC33 molecules. EC33 cannot cross the blood–brain barrier. When RB150 has entered the brain, two active molecules of EC33 are released by brain reductases. The active EC33 molecules binds to the active site of aminopeptidase A (APA) and inhibits the formation of angiotensin III (Ang-III). Ang-III is the effector peptide. Normally Ang-III increases the blood pressure via 3 different mechanisms: (1) increases the release of arginine-vasopressin (AVP), (2) sympathetic nerve activation, and (3) inhibition of the baroreflex. When APA is inhibited, angiotensin II is not cleaved into Ang-III, which exerts a stimulatory action on the control of blood pressure in brain structures, resulting in decreased blood pressure. Abbreviations: aminopeptidase A (APA), angiotensin II (Ang-II), angiotensin III (Ang-III), paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM), nucleus of the solitary tract (NTS), arginine-vasopressin (AVP). Modified from [35].