Mianserin HCl is a tetracyclic compound, with a Ki value of 0.056 ± 0.012µM for 5-HT6R[1]. Mianserin HCl inhibits 5-HT-stimulated [Ca2+]i increase with an IC50 value of 16 ± 3.8nM and suppresses amplification by 5-HT of ADP-induced aggregation of canine platelets with an IC50 value of 3.18µM[2-3]. Mianserin HCl has been widely used to regulate dopamine levels in the prefrontal cortex of animals[4].
In vitro, Mianserin HCl treatment for 72h inhibited the proliferation of SW480 cells with an IC50 value of 37.5μM[5]. Treatment of Hep2 and Huh7 cells with 15μg/ml Mianserin HCl for 72 hours significantly inhibited cell viability and induced cell apoptosis[6].
In vivo, Mianserin HCl treatment via daily intraperitoneal injection at a dose of 2mg/kg for 3 weeks blocked both 5-HT-2 and 5-HT-1A receptors in a rat model of depression[7]. Intra-articular injection of 50μM Mianserin HCl (50μl) into both knees once a week for 8 weeks prevented cartilage degeneration in a rat model of osteoarthritis and inhibited Wnt/β-catenin signaling in articular chondrocytes[8].
References:
[1] Więckowski K, Szałaj N, Gryzło B, et al. Serotonin 5-HT6 receptor ligands and butyrylcholinesterase inhibitors displaying antioxidant activity—design, synthesis and biological evaluation of multifunctional agents against Alzheimer’s disease[J]. International Journal of Molecular Sciences, 2022, 23(16): 9443.
[2] Ohsuka N, Mashiko H, Kaneko M, et al. Effects of Antidepressants and antipsychotics on the 5HT2 receptor-mediated signal transducing system in human platelets[J]. Psychopharmacology, 1995, 121(4): 428-432.
[3] Bush L R. Effects of the serotonin antagonists, cyproheptadine, ketanserin and Mianserin HCl, on cyclic flow reductions in stenosed canine coronary arteries[J]. The Journal of pharmacology and experimental therapeutics, 1987, 240(2): 674-682.
[4] Tanda G, Bassareo V, Chiara D. Mianserin HCl markedly and selectively increases extracellular dopamine in the prefrontal cortex as compared to the nucleus accumbens of the rat[J]. Psychopharmacology, 1996, 123(2): 127-130.
[5] Duan Z, Zhou Z, Lu F, et al. Antitumor activity of Mianserin HCl (a tetracyclic antidepressant) primarily driven by the inhibition of SLC1A5-mediated glutamine transport[J]. Investigational New Drugs, 2022, 40(5): 977-989.
[6] Huang Y H, Yeh C T. Anticancer effects of antidepressants in hepatocellular carcinoma cells[J]. Anticancer research, 2023, 43(3): 1201-1206.
[7] Jotaro A, Kounosuke T, Yuuko M, et al. Effects of chronic Mianserin HCl administration on serotonin metabolism and receptors in the 5-hydroxytryptophan depression model[J]. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1994, 18(1): 165-179.
[8] Okura T, Ohkawara B, Takegami Y, et al. Mianserin HCl suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis[J]. Scientific Reports, 2019, 9(1): 2808.
Mianserin HCl是一种四环类化合物，对5-HT6受体的Ki值为0.056 ± 0.012µM[1]。Mianserin HCl可抑制5-HT刺激的细胞内钙离子（[Ca2+]i）增加（IC50=16 ± 3.8nM），并能抑制由5-HT扩增的ADP诱导的犬血小板聚集（IC50=3.18µM）[2-3]。Mianserin HCl已广泛应用于动物模型中调节前额叶皮质多巴胺水平[4]。
在体外，Mianserin HCl处理72小时可抑制SW480细胞增殖，IC50值为37.5μM[5]。15μg/ml的Mianserin HCl处理Hep2和Huh7细胞72小时能显著抑制细胞活力并诱导凋亡[6]。
在体内，每日以2mg/kg剂量腹腔注射Mianserin HCl持续3周可阻断抑郁模型大鼠额叶皮质5-HT-2和5-HT-1A受体[7]。骨关节炎大鼠模型每周双膝关节腔内注射50μM的Mianserin HCl（50μl）持续8周能预防软骨退化并抑制关节软骨中Wnt/β-catenin信号通路[8]。