Vasopeptidase inhibitors
Vasopeptidase inhibitors are potential drugs that inhibit both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP). As a result of the inhibition of the angiotensin converting enzyme, the formation of the blood vessel- contracting angiotensin II is suppressed and the renin-angiotensin-aldosterone system intervenes. An inhibition of the neutral endopeptidase has a reduction of the breakdown of the natriuretic peptides atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), which an increased urine excretion ( diuresis ) and an expansion of blood vessels ( vasodilatation) ) effect, result. Both mechanisms complement each other synergistically in the sense of lowering blood pressure . Therefore, vasopeptidase inhibitors are being developed as drugs for the treatment of high blood pressure ( antihypertensive drugs ), heart failure and atherosclerosis .
The most advanced vasopeptidase inhibitor was omapatrilat , for which the manufacturing company withdrew the approval applications in 2000. Other vasopeptidase inhibitors such as fasidotrilat , sampatrilat and ilepatrilat have been tested in clinical studies . A drug approval has not yet been granted.
Triple vasopeptidase inhibitors, such as CGS 35601 , represent a further development of the classic dual vasopeptidase inhibitors . They have an additional endothelin converting enzyme 1 (ECE-1) inhibiting effect and thus also lead to a reduction in blood pressure via the endothelin system.
Individual evidence
- ↑ Corti R, Burnett JC, Rouleau JL, Ruschitzka F, Lüscher TF: Vasopeptidase inhibitors: a new therapeutic concept in cardiovascular disease? . In: Circulation . 104, No. 15, October 2001, pp. 1856-62. PMID 11591626 .
- ↑ Blaeser-Kiel, Gabriele: Vasopeptidase inhibition: omapatrilat is being investigated further . Dtsch Arztebl 2000; 97 (48): A-3279 / B-2767 / C-2570 online here
- ↑ Ozdener F, Ozdemir V: Fasidotril Eli Lilly . In: Curr Opin Investig Drugs . 4, No. 9, September 2003, pp. 1113-9. PMID 14582457 .
- ↑ Allikmets K: sampatrilat Shire . In: Curr Opin Investig Drugs . 3, No. 4, April 2002, pp. 578-81. PMID 12090727 .
- ↑ Tabrizchi R: Ilepatril (AVE-7688), a vasopeptidase inhibitor for the treatment of hypertension . In: Curr Opin Investig Drugs . 9, No. 3, March 2008, pp. 301-9. PMID 18311667 .
- ↑ Daull P, Jeng AY, Battistini B: Towards triple vasopeptidase inhibitors for the treatment of cardiovascular diseases . In: J Cardiovasc Pharmacol . 50, No. 3, September 2007, pp. 247-56. doi : 10.1097 / FJC.0b013e31813c6ca5 . PMID 17878751 .