Aliskiren: A novel, orally active renin inhibitor

Abstract

Activation of the renin-angiotensin (Ang)-aldosterone system (RAAS) plays an important role in the development of hypertension and end-organ damage. RAAS suppression is, therefore, an important goal of antihypertensive therapy, and RAAS inhibitors, such as Ang-converting enzyme (ACE) inhibitors and Ang receptor blockers (ARBs), have proven to be highly successful treatments for hypertension, heart failure and related cardiovascular disorders. [1] Although renin was discovered more than a century ago, [2,3] the significance of this system in the pathogenesis of cardiovascular and renal disorders has gained wide acceptance only during the past 3 decades, in large part because of the availability of specific pharmacologic agents that can block the system. [2] The concept of blocking the RAAS at its origin by inhibiting renin has existed for at least 50 years. The first synthetic renin inhibitor was pepstatin, which was followed by first-generation agents that were active but required parenteral administration. Oral agents that were subsequently developed, such as enalkiren, remikiren, and zankiren, had limited clinical use because they demonstrated poor bioavailability (,2%), short half-lives and weak antihypertensive activity. [4] Aliskiren Intensive efforts have been made to discover therapeutic, nonpeptide and orally effective hypertensive drugs. Drugs that

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