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The 5‐HT 2A Receptor Antagonists Pizotifen and Cyproheptadine Inhibit Serotonin‐enhanced Platelet Function
Author(s) -
Lin Olivia,
Espinosa Enma Veronica Paez,
Khasawneh Fadi T
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1096.17
Subject(s) - cyproheptadine , hemostasis , antithrombotic , pharmacology , 5 ht receptor , platelet , medicine , serotonin , bleeding time , receptor , chemistry , platelet aggregation
In an effort to define new agents for antithrombotic purposes, there is an interest in repurposing FDA‐approved drugs as antiplatelet agents. The 5‐HT 2A receptor is a G‐protein coupled receptor (GPCR) expressed on many cell types, including platelets, and a known therapeutic target for many disease states. This erotonin receptor is also known to regulate platelet function. Thus Pizotifen and Cyproheptadine, two antidepressant 5‐HT 2A receptor antagonists, are selected to determine if they can be repurposed and if the 5‐HT 2A receptor can be targeted for antiplatelet activity. The results revealed that Pizotifen and Cyproheptadine reversed serotonin‐enhanced ADP‐induced platelet aggregation. Our study also employed a thrombosis model of the carotid artery, to determine the potential of Pizotifen and Cyproheptadine as thromboprotective agents in vivo . The results show an increased occlusion time after blood vessel injury in mice treated with Pizotifen and Cyproheptadine compared to controls. Finally, the tail‐bleeding time was employed to investigate the effect of Pizotifen and Cyproheptadine on hemostasis. Our findings show prolonged bleeding time in both Pizotifen‐, and Cyproheptadine‐treated mice compared to controls. Collectively, the data indicate that the 5‐HT 2A antagonists Pizotifen and Cyproheptadine have antithrombotic effects, but their use may interfere with normal hemostasis.