Effect of DC-015, a novel potent and selective alpha 1-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 alpha 1-, alpha 2-adrenoceptors and 5-HT1, 5-HT2 receptors were about 0.21 (nM), 0.59 (microM), 0.16 (microM) and 0.38 (microM), respectivity. On the other hand, the Ki values of prazosin for alpha 1- and alpha 2-adrenoceptors were about 0.19 (nM) and 4.8 (microM), respectivity. Experimental results indicated that DC-015 dose-dependently inhibited noradrenaline (10 microM)-induced platelet aggregation in human platelet-rich plasma. At 20 microM, DC-015 would completely inhibit platelet aggregation induced by noradrenaline. A high concentration of prazosin (> 30 mM) caused sligh inhibition of aggregation. Furthermore, DC-015 (2 microM) significantly increased the cyclic AMP level in human platelet-rich plasma, whereas, prazosin significantly increased cyclic AMP level only at higher concentrations (100 microM). We can conclude that DC-015 inhibited noradrenaline-induced platelet aggregation mainly through binding to alpha 2-receptor on platelets, resulting in inhibiting platelet aggregation.
Yen
M H
MH
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lee
Y M
YM
Huang
T F
TF
Sheu
J R
JR
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats
D058668:Adrenergic alpha-1 Receptor Antagonists; D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C100699:DC 015; D011224:Prazosin