Summary
The relationship between the effects of suloctidil in vivo as an antiplatelet agent
and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated.
Suloctidil was found to be effective in reducing platelet aggregates formation in
the retired breeder rat as determined using the platelet aggregate ratio method (PAR)
with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT
depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation
was found between platelet 5- HT content and this antiplatelet activity. Reduction
of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day)
of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered
platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet
5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level.
However, these platelets exhibited a short-lived, significant increase in percent
leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at
high doses may with time result in platelet 5-HT depletion, however this effect is
probably not related to the primary anti-aggregatory activity of the drug.
