Comparison of the pharmacological mechanisms involved in the platelet lowering actions of anagrelide and hydroxyurea: A review

Anagrelide and hydroxyurea have different mechanisms of action and tolerability profiles (Table 1). The primary target of hydroxyurea is ribonucleoside diphosphate reductase, inhibition of which accounts for both the platelet-lowering action and the toxic effects of this compound. In contrast, the known primary target of anagrelide is a Type III phosphodiesterase found in platelets, though it is not apparent that inhibition of this enzyme is involved in the potent platelet-lowering action of this compound. Phosphodiesterase inhibition, however, accounts for the effects of anagrelide on platelet aggregation and may also explain some of the adverse effects of this compound on the function of other cells. While hydroxyurea is a general myelosuppressive agent, anagrelide is a highly selective anti-megakaryocytic agent. The putative leukaemogenic potential of hydroxyurea stems from the fact that it inhibits DNA repair mechanisms and consequently enhances the rate of mutations. Anagrelide, on the other hand, lacks laeukaemogenic and mutagenic properties. In contrast, its main toxicity is cardiovascular, emanating from its vasodilatory and positive inotropic properties.