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

doi:10.1248/bpb.b20-00698

Regular Articles

Antiplatelet Effect of Mirtazapine via Co-blocking of the 5-HT_2A 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

Author information

Yohei Kawano Corresponding author
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Maho Katsuyama
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Masashi Nagata
Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University (TMDU)
Maki Obana
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Satoshi Nakamatsu
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Ayano Mori
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Namiki Sakamoto
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Yasunari Mano
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Kenichi Negishi
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Shuji Shimada
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
Takao Aoyama
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)

Keywords: mirtazapine, platelet, 5-hydroxytryptamine (5-HT)_2A receptor, α₂-adrenergic receptor, bleeding risk

JOURNAL FREE ACCESS FULL-TEXT HTML

2021 Volume 44 Issue 2 Pages 238-244

DOI https://doi.org/10.1248/bpb.b20-00698

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Abstract

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 100 mg/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-HT_2A 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.

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