Study of platelet aggregation in vivo. IX. Effect of nafazatrom on in vivo platelet aggregation and spontaneous tumor metastasis
Ambrus, J.L.; Ambrus, C.M.; Gastpar, H.; Williams, P.
Journal of Medicine 13(1-2): 35-47
1982
ISSN/ISBN: 0025-7850 PMID: 6288824 Document Number: 187329
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 stump-tailed monkeys. In vivo, it was a powerful inhibitor of ADP-induced platelet aggregation as measured by an in vivo platelet aggregation recording instrument described previously. This effect was potentiated by dipyridamole. Following parenteral administration of Bay g 6575, no ex vivo inhibition of ADP, serotonin, epinephrine and collagen-induced platelet aggregation was noticed. 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 was also highly effective as a platelet aggregation inhibitor in monkeys after oral administration. In mice, Bay g 6575 increased circulation time of i.v. 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. No effect was seen in the metastatic rate of NIH renal adenocarcinoma in BALB/cCr mice. [The settling of metastatic tumor cells in the microcirculation may be related to platelet aggregation on the abnormal membranes of these cells. Platelet aggregation inhibitors appear to prevent metastasis.].