Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS).
Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University (TMDU).
Biol Pharm Bull. 2021;44(2):238-244. doi: 10.1248/bpb.b20-00698.
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 and α-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.
米氮平（MTZ）是一种去甲肾上腺素能和特异性 5-羟色胺能抗抑郁药。据报道，MTZ 与出血风险增加有关。然而，其潜在机制尚不清楚。在这项研究中，我们通过透光比浊法研究了 MTZ 在小鼠中的抗血小板作用，以阐明 MTZ 诱导出血的机制。体外研究结果表明，MTZ（20 或 100mg/kg）口服给药可显著抑制 5-羟色胺（5-HT）和肾上腺素协同作用介导的血小板聚集。此外，MTZ 还可显著抑制 ADP 和 5-HT 或肾上腺素协同作用介导的血小板聚集。在 5-HT 和肾上腺素诱导的血小板聚集的体外条件下，也获得了类似的结果。总的来说，这些结果表明，MTZ 通过同时阻断血小板上的 5-HT 和α-肾上腺素能受体发挥抗血小板作用，并抑制由 5-HT 或肾上腺素增加的 ADP 介导的血小板聚集。因此，建议服用 MTZ 的患者详细监测出血情况。
