Markwardt F
Pharmacology, International Institute of Thrombosis, Vascular Diseases, Erfurt-Frienstedt, Germany.
Semin Thromb Hemost. 2001 Oct;27(5):523-30. doi: 10.1055/s-2001-17962.
The progress in molecular biology has stimulated interest in the structure and function of thrombin. It has improved the understanding of its central role in thrombogenesis and has clarified the molecular events of inhibitor binding. This development has resulted in the production of recombinant hirudins and the design of hirudin analogues. It has also allowed the molecular design of synthetic antithrombins and encouraged the development of these products for clinical use. All pharmacological aspects speak in favor of the use of the direct thrombin inhibitors as antithrombotic agents, especially in the potential indications in which thrombin plays a crucial role in the pathogenesis. If their apparent advantages in comparison to glycosaminoglycans can be shown effectively, the direct thrombin inhibitors may become the drug of choice for certain indications.
分子生物学的进展激发了人们对凝血酶结构与功能的兴趣。它增进了对凝血酶在血栓形成中核心作用的理解,并阐明了抑制剂结合的分子事件。这一进展催生了重组水蛭素的生产以及水蛭素类似物的设计。它还使得合成抗凝血酶的分子设计成为可能,并推动了这些产品用于临床的开发。所有药理学方面的情况都表明,直接凝血酶抑制剂作为抗血栓药物是有益的,尤其是在凝血酶在发病机制中起关键作用的潜在适应症方面。如果能有效证明它们相对于糖胺聚糖的明显优势,直接凝血酶抑制剂可能会成为某些适应症的首选药物。