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LB30057 Inhibits Platelet Aggregation and Vascular Relaxation Induced by Thrombin
Byoung-InJung,Kyu-TaeKang,배옥남,Moo-YeolLee,Seung-MinChung,Sang-KooLee,In-ChulKim,Jin-HoChung 대한약학회 2002 Archives of Pharmacal Research Vol.25 No.6
Previous study showed that an amidrazonophenylalanine derivative, LB30057, which has high water solubility, inhibited the catalytic activity of thrombin potently by interaction with the active site of thrombin. In the current investigation, we examined whether LB30057 inhibited platelet aggregation and vascular relaxation induced by thrombin. Treatment with LB30057 to plateletrich plasma (PRP) isolated from human blood resulted in a concentration-dependent inhibition of thrombin-induced aggregation. Values for IC50 and IC100 were 54 ± 4 nM and 96 ± 3 nM, respectively. This inhibition was agonist (thrombin) specific, since IC50 values for collagen and ADP were much greater than those for thrombin. In addition, concentration-dependent inhibitory effects were observed on the serotonin secretion induced by thrombin in PRP. Consistent with these findings, thrombin-induced increase in cytosolic calcium levels was inhibited in a concentration-dependent manner. When LB30057 was treated with aortic rings isolated from rats, LB30057 resulted in a concentration-dependent inhibition of thrombin-induced vascular relaxation. All these results suggest that LB30057 is a potent inhibitor of platelet aggregation and blood vessel relaxation induced by thrombin.
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