XC 386: A new antiplatelet agent |
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Authors: | Jih-Pyang Wang Mei-Feng Hsu Huei-Yann Tsai Li-Jiau Huang Che-Ming Teng |
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Institution: | 1. Department of Pharmacology, China Medical College, Taichung, Taiwan, R.O.C.;2. Department of Biochemistry, China Medical College, Taichung, Taiwan, R.O.C.;3. School of Pharmacy, China Medical College, Taichung, Taiwan, R.O.C.;4. Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C. |
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Abstract: | XC386 was a new antiplatelet compound, which inhibited the aggregation and release reaction of rat platelet-rich plasma induced by collagen. This inhibition was dose-dependent and the IC50was calculated to be 1 mM on collagen-induced aggregation. In washed platelets, the aggregations induced by ADP and collagen were much more markedly inhibited by XC386 than those induced by thrombin, A23187 and arachidonate. High calcium (4 to 8 mM) could not antagonize the inhibition. XC386 did not alter the malondialdehyde (MDA) and thromboxane B (TXB2) levels of resting platelets. But MDA formation induce by collagen, thrombin and A23187, and TXB2 formation induced by collagen and thrombin were significantly inhibited, while both formations induced by arachidonate were not changed. Combination of indomethacin or CP/CPK and XC386 enhanced markedly the inhibitory effect of XC386 on collagen- or A23187-induced aggregation. It was concluded that XC386 might inhibit platelet aggregation before the step of arachidonic acid release by phospholipase A2. |
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Keywords: | XC386 platelet aggregation ATP release |
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