INHIBITION OF SEROTONIN-INDUCED PLATELET AGGREGATION IN RELATION TO THROMBUS PRODUCTION

¹ Smith Kline and French Research Institute, Department of Pharmacology, University of Sydney, Sydney, Australia

The experiments describe the inhibition of platelet aggregation in vitro and the diminished accretion of the artificial thrombus in the Chandler apparatus by 2-bromolysergic acid diethylamide (BOL-148), imipramine, chiorpromazine, diphenhydramine, atropine, l-hyoscyamine and homatropine. 5-Hydroxytryptamine (5-HT) and adenosine diphosphate (ADP) caused platelet aggregation in sheep platelet-rich plasma in concentrations of 1.2 and 1.3 µM, as did thrombin (0.2 U/ml). Aggregation induced by 5-HT was inhibited by BOL-148 (0.02 µM), chlorpromazine (0.03 µM), imipramine (1.3 µM) diphenhydramine (1.9 µM), atropine (3.4 µM), homatropine (4.3 µM) and l-hyoscyamine (5.6 µM) in a selective manner, whereas little if any inhibitory effect was demonstrated by these drugs against ADP clumping. Thrombin aggregation was more susceptible to inhibition than ADP aggregation but less susceptible than 5-HT-induced clumping. Adenosine (1.1 µM) was equally effective in antagonizing 5-HT, ADP and thrombin-induced platelet aggregation. Hyoscine was inactive. In the Chandler tube apparatus the thrombus formation time of recalcified sheep whole blood and platelet-rich plasma was significantly prolonged in the presence of these agents with the exception of hyoscine. These results correlate well with the inhibition of serotonin uptake into platelets by these drugs. Since the thrombin clotting times in platelet-poor plasma were unaffected in their presence, it is suggested that the inhibitory effect of these substances on both platelet clumping and the experimental thrombus development is not an anticoagulant action but that it is related to their ability to prevent the uptake of serotonin by platelets, and that 5-HT may have a secondary and potentiating role in thrombosis.