Aliskiren: A Novel, Orally Active Renin Inhibitor

Renin-angiotensin-aldosterone systems play a major role in the regulation of human homeostasis mechanism, which are also involved in the development of hypertension and end-organ damage through activation of angiotensin II. Inhibitors of the renin-angiotensin-aldosterone system may reduce the development of end-organ damage to a greater extent than other antihypertensive agents. Aliskiren is the first member of the new class of orally active direct renin inhibitors recently approved by the US Food and Drug Administration for the treatment of hypertension. Aliskiren directly inhibiting the renin and reducing the formation of angiotensin II, which is the most effective mediator involved in the pathogenesis of cardiovascular diseases. The present review mainly focuses on the pharmacodynamics and pharmacokinetics and clinical aspects of aliskiren. In this respect, the review will improve the basic idea to understand the pharmacology of aliskiren, which is useful for the further research in cardiovascular disease. inhibit renin have been available for many years but have been limited by low potency, bioavailability and duration of action. However, a new class of nonpeptide, low molecular weight, orally active inhibitors has recently been developed.[5] One drug that emerged from this effort is aliskiren, a direct human-renin inhibitor that blocks the conversion of angiotensinogen to Ang I.[6] Aliskiren [Figure 1], a 2(S), 4(S), 5(S), 7(S)-N-(2-carbamoyl-2methylpropyl)5-amino-4-hydroxy-2,7-diisopropyl-8-(4-methoxy-3[3-meth oxypropoxy-]phenyl)-octanamide, is the only orally active renin inhibitor that has successfully progressed to phase III trials and extensive clinical use.[7,8] The US Food and Drug Administration’s approval in March 2007 of aliskiren, the first commercially available direct renin inhibitor, for the treatment of hypertension met with great enthusiasm. Despite the notable absence of human clinical data for this agent, many clinicians have touted aliskiren as the ideal agent to achieve additional suppression of the RAAS as a means to reduce the morbidity and mortality of chronic diseases of the cardiovascular and renal systems.[5] Figure 1: Structure of aliskiren