Platelet Hypersensitivity to Serotonin After Prolonged Ketanserin Intake?

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Abstract
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 I 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 < 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. C. p < 0.01). The last dose of ketanserin abolished this hyperresponsivencss ID: 46.1 + 7.58: C vs. D. p 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 hyper-responsiveness 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.

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