Anti-aggregatory drugs: I. Platelet receptor antagonists

Abstract

The inhibition of platelet aggregation is a major task for the prevention and treatment of cardiovascular diseases. The increasing necessity for efficient anti-aggregatory treatment calls for drugs with specific characteristics, namely: fast onset of action, reversibility, negligible adverse effects, high specificity and efficacy. These prerequisites can be met with specific receptor antagonists. In the last few years many platelet receptors have been identified, cloned, expressed and characterised initiating a new direction in the development of anti-aggregatory drugs. The progress in receptor research enabled the development of novel, highly specific antiplatelet drugs. Receptor-targeted treatment offers several advantages over classical anti-aggregatory treatment. The principal advantages of these novel platelet receptor inhibitors are their high specificity and the reversibility of their inhibitory effect. At present receptor antagonists for many platelet receptors are available, some are already successfully used in the clinic (e.g., adhesion receptor inhibitors and ADP receptor antagonists), others have just entered clinical trials. Antagonists to receptors for adhesion proteins, ADP and thromboxane are particularly promising drugs for anti-aggregatory treatment. Nevertheless, some receptor antagonists, mainly the antibodies and peptidic antagonists, bear one fundamental disadvantage: their low stability means that they require iv. or sc. drug administration. For preventive treatment after cardiovascular events or clinical intervention prolonged treatment is necessary for which oral drug administration with stable drugs or prodrugs is desirable. Some of the new drugs could not fulfil the expectations set in them. Here studies showed that combinations of receptor antagonists with other inhibitors might provide more potent drugs.

• antiplatelet drugs
• platelet aggregation
• platelet receptors
• receptor antagonists