[Inhibition of platelet function by KB-2796].
The anti-platelet activity of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4- (2,3,4-trimethoxybenzyl) piperazine dihydrochloride, was studied in guinea pigs and mice. When guinea pig platelet-rich plasma (PRP) was employed, platelet function was inhibited at high doses of KB-2796. The IC50 value for [3H]5-HT release was 940 microM, and the IC50 values for collagen- and ADP-induced platelet aggregation were 210 and 390 microM, respectively. Oral administration of KB-2796 at 10-100 mg/kg dose-dependently inhibited the transient thrombocytopenia induced by collagen, but not that caused by ADP. KB-2796 protected mice from death after intravenous injection of collagen plus epinephrine, with an ED50 value of 9.5 mg/kg, p.o. Oral administration of KB-2796 at 10-100 mg/kg dose-dependently reduced guinea pig platelet retention in glass bead columns and reduced the leakage of ADP and ATP from erythrocytes passing through similar columns. KB-2796, at a concentration of 1-10 microM, produced a stabilizing effect on guinea pig erythrocytes against hypotonic hemolysis. These results suggest that KB-2796 is an inhibitor of platelet function and that its inhibition is related mainly to the inhibition of leakage of ADP and ATP from erythrocytes.
Yamamoto
N
N
New Drug Research Laboratories, Kanebo Ltd., Osaka, Japan.
Yokota
K
K
Yamashita
A
A
Ito
K
K
D000284:Administration, Oral; D000818:Animals; D003094:Collagen / Q000037:antagonists & inhibitors; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013923:Thromboembolism / Q000188:drug therapy
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D003094:Collagen; C052424:lomerizine