Study of platelet aggregation in vivo. IX. Effect of nafazatrom on in vivo platelet aggregation and spontaneous tumor metastasis.
Nafazatrom (Bay g 6575) was explored for its ability to inhibit platelet aggregation. In vitro, it had no effect on ADP, serotonin, epinephrine, or collagen induced platelet aggregation in platelet rich plasma of monkeys. On the other hand, in vivo it was a powerful inhibitor of ADP induced platelet aggregation as measured by the in vivo platelet aggregation recording instrument described previously (Ambrus et al., 1976). This effect was potentiated by dipyridamole. On the other hand, following parenteral administration of Bay g 6575, no ex vivo inhibition was noticed of ADP, serotonin, epinephrine, and collagen induced platelet aggregation. The hypothesis was presented that Bay g 6575 acts by increasing prostacyclin synthesis and/or release or interferes with its decomposition. This may explain in vivo activity; rapid decomposition may explain inability to demonstrate ex vivo activity. This also explains potentiation by the phosphodiesterase inhibitor dipyridamole. Bay g 6575 also was highly effective as a platelet aggregation inhibitor in monkeys after oral administration. In mice, Bay g 6575 increased circulation time of intravenously injected polyploid Ehrlich ascites tumor cells. In Furth-Wistar rats implanted with Furth-Columbia Wilms' tumor, in A/J mice implanted with C1300 neuroblastoma and in Wistar rats implanted with SMT-2A (Kim) breast cancer, Bay g 6575 significantly reduced spontaneous pulmonary metastasis. On the other hand, no effect was seen in the metastatic rate of NIH renal adenocarcinoma in BALB/cCr mice.
D000230:Adenocarcinoma / Q000503:physiopathology; D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology; D002286:Carcinoma, Ehrlich Tumor / Q000503:physiopathology; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000503:physiopathology; D008175:Lung Neoplasms / Q000556:secondary; D008251:Macaca; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000503:physiopathology; D009360:Neoplastic Cells, Circulating; D009447:Neuroblastoma / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D047069:Pyrazolones; D051381:Rats; D009396:Wilms Tumor / Q000503:physiopathology
D005343:Fibrinolytic Agents; D011720:Pyrazoles; D047069:Pyrazolones; C018845:nafazatrom