Antiplatelet effect of mirtazapine via co-blocking of the 5-HT2A and α2-adrenergic receptors on platelets

Yohei Kawano, Maho Katsuyama, Masashi Nagata, Maki Obana, Satoshi Nakamatsu, Ayano Mori, Namiki Sakamoto, Yasunari Mano, Kenichi Negishi, Shuji Shimada, Takao Aoyama

Research output: Contribution to journalArticlepeer-review


Mirtazapine (MTZ) is a noradrenergic and specific serotonergic antidepressant. MTZ is reportedly associated with an increased risk of bleeding. However, the underlying mechanism remains unclear. In this study, we investigated the antiplatelet effect of MTZ in mice via light transmission aggregometry to elucidate the mechanism of MTZ-induced bleeding. The results of the ex vivo study showed that the oral administration of MTZ (20 or 100mg/kg) significantly suppressed platelet aggregation mediated by the synergic interaction of 5-hydroxytryptamine (5-HT) and adrenaline. Additionally, MTZ significantly suppressed platelet aggregation, mediated by the synergic interaction of ADP and 5-HT or adrenaline. Similar results were obtained in vitro, under the condition of 5-HT- and adrenaline-induced platelet aggregation. Overall, the results suggest that MTZ exerts antiplatelet effect by co-blocking 5-HT2A and α2-adrenergic receptors on platelets and suppresses platelet aggregation mediated by ADP, increased by either 5-HT or adrenaline. Thus, a detailed monitoring of bleeding is recommended for patients taking MTZ.

Original languageEnglish
Pages (from-to)238-244
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Issue number2
Publication statusPublished - 1 Feb 2021


  • 5-hydroxytryptamine (5-HT) receptor
  • Bleeding risk
  • Mirtazapine
  • Platelet
  • α-adrenergic receptor

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