Platelet hypersensitivity to serotonin after prolonged ketanserin intake?

In the present study the effect of acute and short-term ketanserin administration on serotonin (5-HT)-induced aggregation was investigated in eight healthy volunteers. They received 40 mg ketanserin three times a day for 1 week. Blood samples were drawn before (A), 1.5 h after the first dose (B), 12 h after the evening dose of the 7th day (C), and 1.5 h after the morning dose of the 8th day (D). The maximal rate of aggregation (mm/min +/- SEM) was significantly decreased following the first dose (A: 47.6 +/- 6.0; B: 27.6 +/- 4.5; p less than 0.05); 12 h after the evening dose of the 7th day, the platelets aggregated more rapidly with 5-HT than before the onset of the study (C: 69.4 +/- 6.0; A vs. p less than 0.01). The last dose of ketanserin abolished this hyperresponsiveness (D: 46.1 +/- 7.58; C vs. D, p less than 0.05); however, there was no significant difference in the velocity of aggregation between the onset of the study and after the last dose. It appears that ketanserin has a double effect on platelet aggregation: an initial hyporesponsiveness to 5-HT is followed by a delayed hyperresponsiveness that is temporarily corrected by renewed ketanserin intake. In vitro dose-response curves suggested that prolonged ketanserin intake results in a higher "sensitivity" of the platelets to serotonin rather than a refractoriness of the platelets to ketanserin.