Cort J H, Schwartz I L
Yale J Biol Med. 1978 Nov-Dec;51(6):605-14.
Natural vasopressins have been used, with varying success, in attempts to stop bleeding from esophageal varices for over two decades. Reasons for lack of success include (a) failure to induce a sufficiently prolonged and constant vasoconstrictor effect at the bleeding site, (b) dangerous side-effects, and (c) release of plasminogen activator induced by the peptides which can lyse any clot as it forms.IN THE LAST DECADE ANALOGS OF VASOPRESSIN HAVE BEEN DEVELOPED WITH A PROLONGED ACTION, USING TWO SEPARATE PRINCIPLES OF CHEMICAL MODIFICATION: (1) hormonogens, and (2) blockage of sites of inactivating enzymatic cleavage (in particular "carba" analogs without a disulfide bridge). These two categories of analog are compared here: the carba analogs have the advantages of high potency (higher than the parent hormone) with prolongation, but are also very active on the plasminogen activator release system. The hormonogens combine prolongation with low potency, but have lost not only a releasing action on plasminogen activator, but also, by virtue of altered release kinetics, have effectively lost cardiovascular toxicity.Mechanisms of analog action and receptor interaction are presented, along with initial clinical experiences.
二十多年来，人们一直使用天然血管加压素试图阻止食管静脉曲张出血，但效果各异。治疗失败的原因包括：（a）未能在出血部位诱导出足够持久和恒定的血管收缩作用；（b）存在危险的副作用；（c）这些肽可诱导纤溶酶原激活物的释放，从而能溶解形成的任何血凝块。在过去十年中，人们利用两种不同的化学修饰原理开发出了作用时间延长的血管加压素类似物：（1）激素原；（2）阻断失活酶切位点（特别是没有二硫键的“卡巴”类似物）。本文对这两类类似物进行了比较：卡巴类似物具有强效（比母体激素更强）且作用时间延长的优点，但对纤溶酶原激活物释放系统也非常活跃。激素原兼具作用时间延长和低活性的特点，但不仅失去了对纤溶酶原激活物的释放作用，而且由于释放动力学的改变，实际上也失去了心血管毒性。本文介绍了类似物的作用机制和受体相互作用，以及初步的临床经验。
