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

M. H. Yen, Y. M. Lee, T. F. Huang, J. R. Sheu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalChinese Journal of Physiology
Volume38
Issue number2
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Prazosin
Platelet Aggregation
Adrenergic Receptors
Norepinephrine
Platelet-Rich Plasma
Cyclic AMP
Serotonin 5-HT1 Receptors
Quinazolines
DC 015
Blood Platelets

Keywords

  • α-adrenoceptor
  • DC-015
  • platelet aggregation

ASJC Scopus subject areas

  • Physiology

Cite this

Effect of DC-015, a novel potent and selective α1-adrenoceptor antagonist, comparison with prazosin on noradrenaline-induced platelet aggregation. / Yen, M. H.; Lee, Y. M.; Huang, T. F.; Sheu, J. R.

In: Chinese Journal of Physiology, Vol. 38, No. 2, 1995, p. 93-98.

Research output: Contribution to journalArticle

@article{8f6b69b148944999a499354311d2e79e,
title = "Effect of DC-015, a novel potent and selective α1-adrenoceptor antagonist, comparison with prazosin on noradrenaline-induced platelet aggregation",
abstract = "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.",
keywords = "α-adrenoceptor, DC-015, platelet aggregation",
author = "Yen, {M. H.} and Lee, {Y. M.} and Huang, {T. F.} and Sheu, {J. R.}",
year = "1995",
language = "English",
volume = "38",
pages = "93--98",
journal = "Chinese Journal of Physiology",
issn = "0304-4920",
publisher = "Chinese Physiological Society",
number = "2",

}

TY - JOUR

T1 - Effect of DC-015, a novel potent and selective α1-adrenoceptor antagonist, comparison with prazosin on noradrenaline-induced platelet aggregation

AU - Yen, M. H.

AU - Lee, Y. M.

AU - Huang, T. F.

AU - Sheu, J. R.

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

KW - α-adrenoceptor

KW - DC-015

KW - platelet aggregation

UR - http://www.scopus.com/inward/record.url?scp=0028806973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028806973&partnerID=8YFLogxK

M3 - Article

C2 - 8697903

AN - SCOPUS:0028806973

VL - 38

SP - 93

EP - 98

JO - Chinese Journal of Physiology

JF - Chinese Journal of Physiology

SN - 0304-4920

IS - 2

ER -