Comparison of antiplatelet effects of FK409, a spontaneous nitric oxide releaser, with those of TRK-100, a prostacyclin analogue.
The anti-platelet effects of FK409 ((+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide) , a new spontaneous nitric oxide releaser, and TRK-100 (sodium dl-4-[(1R,2R,3aS,8bS)-1,2,3a,8b-tetra-hydro-2-hydroxy-1-[(3S ,4RS)-3-hydroxy- 4-methyl-oct-6-yen-(E)-1-enyl]-5-cyclopenta[b]benzofuranyl]butyrate), a stable prostacyclin analogue, were studied both in vivo and in vitro. FK409 and TRK-100 inhibited ADP-induced platelet aggregation in rat platelet-rich plasma at 1.0 and 0.032 microM, respectively. In a rat extracorporeal shunt model, FK409 suppressed thrombus formation dose dependently and significantly at 1.0 mg/kg and showed the maximum inhibition (52% inhibition) at 10 mg/kg. TRK-100 showed 79% inhibition of thrombus formation at 1.0 mg/kg, but not at less than 1.0 mg/kg. At the doses required for antiplatelet effects, TRK-100 decreased mean blood pressure significantly but FK409 did not alter the blood pressure. These data suggest that FK409 shows more selective activities on platelets than TRK-100 in these experiments.
Hirasawa
Y
Y
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Nishio
M
M
Maeda
K
K
Yoshida
K
K
Kita
Y
Y
D000244:Adenosine Diphosphate / Q000633:toxicity; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009574:Nitro Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000188:drug therapy
D009574:Nitro Compounds; D010975:Platelet Aggregation Inhibitors; C048081:beraprost; D000244:Adenosine Diphosphate; C061872:FK 409; D011464:Epoprostenol