Effects of ketanserin and mepyramine on platelet aggregation and on the uptake of 5-hydroxytryptamine into platelets.

We have determined the effects of ketanserin, a 5HT2 antagonist, and of mepyramine, a histamine H1 antagonist, on the aggregation induced in platelet rich plasma by 5-hydroxytryptamine (5HT), adenosine diphosphate (ADP), and by combinations of 5HT and ADP. Both ketanserin and mepyramine inhibited 5HT-induced aggregation and the 5HT component of the aggregation induced by combinations of 5HT and ADP. Both agents also inhibited the second phase of the aggregation induced by ADP alone but higher concentrations of the agents were required. On a molar basis, ketanserin was always a more potent inhibitor of aggregation than mepyramine. Ketanserin did not consistently inhibit the ADP-induced release reaction nor did it inhibit ADP-induced aggregation in aspirin-treated platelets that were unable to undergo a release reaction. The results suggest that 5HT2 receptors are involved in 5HT-induced aggregation and that the platelets' endogenous 5HT may contribute to the second phase of ADP-induced aggregation. We have also compared the effects of ketanserin and mepyramine on 5HT uptake into platelets. In this case mepyramine was a much more potent inhibitor than ketanserin. The different effectiveness of ketanserin and mepyramine as inhibitors of aggregation and 5HT uptake provides further evidence for different 5HT receptors for these two processes, and indicates that those involved in the 5HT uptake may be more akin to histamine H1 receptors.