Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) that inhibits 5‐HT2A, 5‐HT2B, 5‐HT2C, and 5‐HT3 receptors, with pKi values of 8.2, 6.7, 7.9 and 8.1, respectively. Mirtazapine can inhibit the presynaptic alpha-2-adrenergic receptors, and induce the release of norepinephrine and serotonin[2].
In vitro, Mirtazapine treatment at 10μM for 24h in SAS-H1 cells increased Lin-7C/β-catenin pathway activity, resulting in a decrease in cell migration[3]. Mirtazapine treatment at 10μM for 24h resulted in a rapid decrease in mouse hepatic B cell numbers and altered hepatic B1a and B2 subgroup profiles, increased CXCL10 levels, and upregulated CXCR3 expression by intrahepatic B cells[4]. Pretreatment of SH-SY5Y cells with 2μM Mirtazapine for 24 hours inhibited H2O2-induced cell death, decreased p53 mRNA expression, and increased Bcl-2/Bax protein ratio[5].
In vivo, Mirtazapine (16mg/kg) administered intraperitoneally to mouse models of Parkinson’s disease once daily for 8 days significantly reduced the loss of dopaminergic neurons on the injured side and promoted astrocyte proliferation and MT-1/2 up-regulation in the striatum[6]. Daily oral administration of 10mg/kg Mirtazapine in CT26/luc colon carcinoma-bearing mouse model for 67 days resulted in a significant reduction in tumor volume[7].
References:
[1] Anttila S A K, Leinonen E V J. A review of the pharmacological and clinical profile of mirtazapine[J]. CNS drug reviews, 2001, 7(3): 249-264.
[2] Park Y S, Oh H, Sung K W. Atypical antidepressant mirtazapine inhibits 5-hydroxytryptamine3 receptor currents in NCB-20 cells[J]. Journal of Pharmacological Sciences, 2023, 151(2): 63-71.
[3] Uzawa K, Kasamatsu A, Shimizu T, et al. Suppression of metastasis by mirtazapine via restoration of the Lin-7C/β-catenin pathway in human cancer cells[J]. Scientific reports, 2014, 4(1): 5433.
[4] Almishri W, Davis R P, Shaheen A A, et al. The antidepressant mirtazapine rapidly shifts hepatic b cell populations and functional cytokine signatures in the mouse[J]. Frontiers in Immunology, 2021, 12: 622537.
[5] Lieberknecht V, Engel D, Rodrigues A L S, et al. Neuroprotective effects of mirtazapine and imipramine and their effect in pro-and anti-apoptotic gene expression in human neuroblastoma cells[J]. Pharmacological Reports, 2020, 72(3): 563-570.
[6] Kikuoka R, Miyazaki I, Kubota N, et al. Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection[J]. Scientific reports, 2020, 10(1): 20698.
[7] Fang C K, Chen H W, Chiang I T, et al. Mirtazapine inhibits tumor growth via immune response and serotonergic system[J]. PloS one, 2012, 7(7): e38886.
Mirtazapine是一种去甲肾上腺素能和特异性血清素抗抑郁药（NaSSA），可抑制5-HT2A、5-HT2B、5-HT2C和5-HT3受体，pKi值分别为8.2、6.7、7.9和8.1[1]。Mirtazapine通过抑制突触前alpha2-肾上腺素能受体，促进去甲肾上腺素和血清素的释放[2]。
在体外，10μM的Mirtazapine处理SAS-H1细胞24小时可增强Lin-7C/β-catenin通路活性，抑制细胞迁移[3]。10μM的Mirtazapine处理小鼠肝脏B细胞24小时会快速减少B细胞数量，改变肝脏B1a和B2亚群分布，提高CXCL10水平并上调肝内B细胞的CXCR3表达[4]。2μM的Mirtazapine预处理SH-SY5Y细胞24小时能抑制H2O2诱导的细胞死亡，降低p53 mRNA表达，并提高Bcl-2/Bax蛋白比例[5]。
在体内，帕金森病模型小鼠每日腹腔注射Mirtazapine（16mg/kg）连续8天，可显著减少损伤侧多巴胺能神经元丢失，并促进纹状体星形胶质细胞增殖及MT-1/2上调[6]。在携带 CT26/luc 结肠癌的实验小鼠模型中，每日口服给予10mg/kg剂量的Mirtazapine，持续 67 天，导致肿瘤体积显著减小[7]。