title: Aliskiren, the first direct renin inhibitor for treatment of hypertension: the path of its development.
abstract: Standard treatments available today for treating hypertension is diuretics, β-blockers, angiotensin converting enzyme inhibitors (ACEs), angiotensin receptor blockers (ARBs), calcium channel blockers, a-blockers, vasodilators, and centrally acting drugs. It is difficult to achieve the optimized renin angiotensin aldosterone system suppression with currently available antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate the compensatory feedback mechanism that increases renin release and increase plasma renin activity. The first orally active direct renin inhibitors (DRIs) were developed in 1980s, including enalkiren, remikiren, and zankiren. However, poor absorption from the gastrointestinal tract, less bioavailability (<2%), short half life, and low potency hindered the development of these compounds. Aliskiren is the first DRI for the treatment of hypertension. Aliskiren is designed through a combination of molecular modeling techniques and crystal structure elucidation. Aliskiren effectively reduces the blood pressure as a mono therapy as well in combination therapy.
authors.affiliation: Department of Infectious Diseases (MUHS), Seth GS Medical College and KEM Hospital, Parel, Mumbai, India. manojpjadhav@yahoo.com
authors.forename: M
authors.initials: M
authors.lastname: Jadhav
authors.forename: C
authors.initials: C
authors.lastname: Yeola
authors.forename: G
authors.initials: G
authors.lastname: Zope
authors.forename: A
authors.initials: A
authors.lastname: Nabar
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005650:Fumarates / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren