Historical perspective of the development of thrombin inhibitors.

Progress in molecular biology has stimulated interest in the structure and function of thrombin. It has improved our 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 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 direct thrombin inhibitors as antithrombotic agents, especially in the potential indications where thrombin plays a crucial pathogenetic role. If their apparent advantages compared with heparin can be definitely demonstrated, the direct thrombin inhibitors may become the drug of choice for certain indications.