Effect of DC-015, a novel potent and selective α1-adrenoceptor antagonist, comparison with prazosin on noradrenaline-induced platelet aggregation

The antiplatelet activity of DC-015, a newly synthesized quinazoline derivative was determined in human platelet-rich plasma. From the binding studies, the Ki values of DC-015 for α₁-, α₂-adrenoceptors and 5-HT₁, 5-HT₂ receptors were about 0.21 (nM), 0.59 (μM), 0.59 (μM) and 0.38 (μM), respectively. On the other hand, the Ki values of prazosin for α₁- and α₂-adrenoceptors were about 0.19 (nM) and 4.8 (μM), respectively. Experimental results indicated that DC-015 dose-dependently inhibited noradrenaline (10 μM)-induced platelet aggregation in human platelet-rich plasma. At 20 μM, DC-015 would completely inhibit platelet aggregation induced by noradrenaline. A high concentration of prazosin (>30 mM) caused slight inhibition of aggregation. Furthermore, DC-015 (2 μM) significantly increased the cyclic AMP level in human platelet-rich plasma, whereas, prazosin significantly increased cyclic AMP level only at higher concentrations (100 μM). We can conclude that DC-015 inhibited noradrenaline-induced platelet aggregation mainly through binding to α₂-receptor on platelets, resulting in inhibiting platelet aggregation.