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.