Antiplatelet and antithrombotic activity of L-3-n-butylphthalide in rats.
3-n-butylphthalide (NBP) is a potentially beneficial drug for the treatment of ischemic stroke with multiple actions on different pathophysiological processes. In the present study, the effect of l-, d-, and dl-NBP was investigated on ADP-, collagen-, and AA-induced platelet aggregation. l-NBP was the most potent among l-, d-, and dl-NBP. At higher concentration the effect of dl-NBP on platelet aggregation was greater than that of l- or d-NBP alone. The ex vivo antiaggregatory activity of l-NBP 100mg/kg declined gradually after 2 hours, but a considerable antiplatelet activity was still observed 4h after l-NBP administration. NBP was given orally and resulted in a dose-dependent inhibition of thrombus formation. Of the two isomers, l-NBP was the most potent. It significantly protected mice from a mixture of collagen and epinephrine induced thromboembolic death. When 100 mg/kg of l-NBP were administered orally to rats, the bleeding time increased 2.1-fold compared with the control group. At the same dose, ex vivo platelet aggregation induced by ADP, collagen, and AA was inhibited by l-NBP and the antithrombotic effects of the compound were also observed. Thus, NBP exerts oral anti-platelet and anti-thrombotic efficacy without perturbing systemic hemostasis in rats. l-NBP is more potent than d- and dl-NBP as antiplatelet agent.
Peng
Ying
Y
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Zeng
Xianke
X
Feng
Yipu
Y
Wang
Xiaoliang
X
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001760:Bleeding Time / Q000379:methods; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000188:drug therapy
D001572:Benzofurans; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; C027125:3-n-butylphthalide