Renin inhibitor

Renin inhibitor
Drug class
Aliskiren
Aliskiren,[1] the first renin inhibitor to be marketed
Class identifiers
UseHypertension
ATC codeC09XA
Biological targetRenin
Clinical data
Drugs.comDrug Classes
Legal status
In Wikidata

Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I,[2][3][4] which in turn reduces the formation of angiotensin II that facilitates blood pressure.[5][6]

Renin inhibitor is often preceded by direct, called direct renin inhibitor in order to distinguish its mechanism from other renin–angiotensin–aldosterone system-interfering drugs such as angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and aldosterone receptor antagonists.[6]

These drugs inhibit the first and rate-limiting step of the renin–angiotensin–aldosterone system (RAAS), namely the conversion of angiotensinogen to angiotensin I. This leads to a totality in absence of angiotensin II based on the rationale that renin only acts to inhibit this step unlike Angiotensin Converting Enzyme which is also involved in other biochemical reactions. Since the 1970s, scientists have been trying to develop potent inhibitors with acceptable oral bioavailability.[7][8] The process was difficult and took about three decades. The first and second generations faced problems such as poor bioavailability and lack of potency. Finally, the third generation was discovered. These compounds were nonpeptidic renin inhibitors, had acceptable oral bioavailability and were potent enough for clinical use. The first drug in this class was aliskiren, which received a marketing approval in 2007.[7] As of June 2020, it is the only renin inhibitor on the market.

  1. ^ Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP (March 2005). "Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients". Circulation. 111 (8): 1012–8. doi:10.1161/01.CIR.0000156466.02908.ED. PMID 15723979.
  2. ^ "Renin Inhibitors". CV Pharmacology. Retrieved 2020-07-22.
  3. ^ Nakano, Stephanie J.; Everitt, Melanie D. (2018). "Neurohormonal Axis and Natriuretic Peptides in Heart Failure". Heart Failure in the Child and Young Adult. Elsevier. pp. 75–86. doi:10.1016/b978-0-12-802393-8.00006-5. ISBN 978-0-12-802393-8.
  4. ^ "The Renin-Angiotensin-Aldosterone-System". TeachMePhysiology. 2020-04-28. Retrieved 2020-07-22.
  5. ^ Nussberger, Jürg (2005). "Renin Inhibitors". Hypertension. Elsevier. pp. 754–764. doi:10.1016/b978-0-7216-0258-5.50162-9. ISBN 978-0-7216-0258-5.
  6. ^ a b Lambers Heerspink, Hiddo J.; Fioretto, Paola; de Zeeuw, Dick (2014). "Pathogenesis, Pathophysiology, and Treatment of Diabetic Nephropathy". National Kidney Foundation Primer on Kidney Diseases. Elsevier. pp. 222–234. doi:10.1016/b978-1-4557-4617-0.00025-x. ISBN 978-1-4557-4617-0.
  7. ^ a b Jensen, C.; Herold, P.; Brunner, H. R. (2008). "Aliskiren: The first renin inhibitor for clinical treatment". Nature Reviews Drug Discovery. 7 (5): 399–410. doi:10.1038/nrd2550. PMID 18340340. S2CID 19633316.
  8. ^ Gross, F.; Lazar, J.; Orth, H. (1972). "Inhibition of the renin–angiotensinogen reaction by pepstatin". Science. 175 (22): 656. Bibcode:1972Sci...175..656G. doi:10.1126/science.175.4022.656. PMID 4109853. S2CID 8348522.