Antithrombotic effects of YS-49 and YS-51--1-naphthylmethyl analogs of higenamine.
The antiplatelet and antithrombotic effects of YS-49 and YS-51--l-naphthylmethyl analogs of higenamine, which is a benzyl-tetrahydroisoquinoline alkaloid isolated from Aconitum japonicum (Ranunculaceae)--were investigated. YS-49 and YS-51 showed inhibitory activities to both human and rat platelet aggregation induced by ADP, collagen and epinephrine. They were more inhibitory to epinephrine-induced aggregation (IC(50); 3.4 and 1.7 microM of YS-49, and 6.0 and 6.3 microM of YS-51 to human and rat platelets, respectively) than ADP- or collagen-induced aggregation. The antithrombotic effects of YS-49 and YS-51 were also observed in both mouse acute thrombosis model and rat arterio-venous shunt (AV shunt) model. The oral administration of YS-49 and YS-51 (50 or 100 mg/kg) increased the recovery rates from the acute thrombotic challenge in mice and lowered the weight of thrombus formed inside the AV shunt tube in rats.
Yun-Choi
H S
HS
Natural Products Research Institute, Seoul National University, Seoul 110-460, South Korea. hsyun@sna.ac.kr
Pyo
M K
MK
Park
K M
KM
Chang
K C
KC
Lee
D H
DH
D000470:Alkaloids; D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines; D013927:Thrombosis / Q000188:drug therapy* / Q000517:prevention & control; D016896:Treatment Outcome
C495109:1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline; D000470:Alkaloids; D005343:Fibrinolytic Agents; D007546:Isoquinolines; D010975:Platelet Aggregation Inhibitors; D044005:Tetrahydroisoquinolines; C090309:YS 49; C012348:higenamine