Jadhav M, Yeola C, Zope G, Nabar A
Department of Infectious Diseases (MUHS), Seth GS Medical College and KEM Hospital, Parel, Mumbai, India.
J Postgrad Med. 2012 Jan-Mar;58(1):32-8. doi: 10.4103/0022-3859.93250.
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.
目前用于治疗高血压的标准疗法包括利尿剂、β受体阻滞剂、血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体阻滞剂（ARB）、钙通道阻滞剂、α受体阻滞剂、血管扩张剂和中枢作用药物。使用目前可用的抗高血压药物难以实现肾素-血管紧张素-醛固酮系统的最佳抑制，因为ACEI、ARB和利尿剂都会激活增加肾素释放并提高血浆肾素活性的代偿性反馈机制。第一代口服活性直接肾素抑制剂（DRI）于20世纪80年代研发，包括依那吉仑、瑞米吉仑和扎尼吉仑。然而，胃肠道吸收差、生物利用度低（<2%）、半衰期短和效力低阻碍了这些化合物的研发。阿利吉仑是首个用于治疗高血压的DRI。阿利吉仑是通过分子建模技术和晶体结构解析相结合设计而成的。阿利吉仑作为单一疗法以及联合疗法均能有效降低血压。
