Effects of ketanserin, a selective 5-HT2 serotonergic antagonist, on the secondary recruitment of human plateletsin vitro

Abstract

Ketanserin, a selective 5-HT2 serotonergic receptor antagonist, reduces in vitro the release-associated human platelet aggregation induced by threshold concentrations of collagen and curtails the second wave of aggregation/release induced by critical concentrations of ADP in particular and, to a lesser extent, of 1-epinephrine. Its inhibitory effect on the second waves becomes more pronounced when the reaction is already attenuated by moderate cyclo-oxygenase inhibition with esculetin, by yohimbine or by propranolol. The first wave of aggregation induced by ADP or 1-epinephrine is not affected. Such an inhibition of secondary platelet recruitment by ketanserin in vitro may be due to an inhibition of the 5-HT2 receptor-mediated amplifying effects of platelet-released 5-HT or to a non-specific interference with the platelet membrane, reducing the release of mediators from the platelets. Reduction of the increased plasma BTG levels in patients after ketanserin may result from such release-inhibiting mechanisms.

Influence of Ethanol and Serotonin on Rat Platelet Aggregation

“…It amplifies platelet aggregation via 5-HT2 receptors, for which ketanserin is a specific antagonist [9]. We found that ethanol considerably ampli fied the action of serotonin in the process of platelet aggregation.…”

“…It has been suggested that ethanol directly affects the function of blood platelet mem branes and acts indirectly by influencing plasma lipids or by changing the release and synthesis of some arachidonic acid deriva tives [2,5,6). Platelets contain serotonin (5-hydroxytryptamine, 5-HT) which evokes in vitro a reversible aggregation of human blood platelets [7] and amplifies platelet ag gregation in response to various agonists in cluding ADP, adrenaline, noradrenaline, collagen and the calcium ionophore A23187 [8], The amplification of platelet aggrega tion by 5-HT is inhibited by the selective 5-HT2 receptor antagonist ketanserin [9], Our previous studies demonstrated [10] that eth anol inhibits the uptake and enhances the release of 5-HT from rat blood platelets. In vitro, it inhibited the aggregation of blood platelets but did not change the potentiating action of 5-HT on ADP-induced aggrega tion.…”

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

“…The inhibitory effect of ketanserin (5-HT 2 receptor antagonist) on the second phase of ADP-aggregation wave became more pronounced when the reaction was already attenuated by PRO [25]. Treatment of rabbits with phenoxybenzamine, resulting in decreased number ofreceptors, was found to decrease aggregation both in the presence and absence of PRO [26].…”

The Serotonergic Mechanisms Are Not Involved in the Inhibitory Effect of Captopril on Rat Platelet Aggregation

“…It amplifies platelet aggregation of rats and hu mans via 5-HT2 receptors [7,8], of which a selective antagonist is ketanserin [14], Thus we tried to determine whether the serotoner gic mechanisms play any role in the suppres sion of platelet aggregation evoked by capto pril. In our experiments we demonstrated that captopril, in contrast to ketanserin, did not affect the amplifying effect of 5-HT ( fig.…”