Selegiline hydrochloride is a selective monoamine oxidase B inhibitor used in the treatment of Parkinson's disease and major depressive disorder[1]. Selegiline hydrochloride can reduce the degradation of dopamine, thereby increasing dopamine levels in the brain[2]. Selegiline hydrochloride also has a variety of biological functions, including the regulation of lipid metabolism and immune responses[3-4].
In vitro, treatment of androgen-insensitive (PC-3, DU145) and androgen-sensitive (22Rv1, LNCaP, VCaP) prostate adenocarcinoma cell lines with Selegiline hydrochloride (100μM–10mM) for 48 hours significantly reduced cell viability and proliferation and enhanced the combined efficacy of anti-androgen drugs and cytostatic agents[5]. Treatment of MCF-7 breast cancer cells, PC12 neuronal pheochromocytoma cells, and THP-1 monocytic cells with Selegiline hydrochloride (0–100μg/ml) for 24 hours significantly induced apoptosis and inhibited cell proliferation while reducing the phosphorylation levels of protein kinase C (PKC)[6].
In vivo, Selegiline hydrochloride (0.6mg/kg) administered intraperitoneally every other day for 6 weeks to C57BL/6 mice induced by a high-fat diet significantly reduced weight gain, liver index, and visceral/subcutaneous fat index, improved dyslipidemia, and decreased serum triglycerides, cholesterol, and low-density lipoprotein levels. Meanwhile, Selegiline hydrochloride significantly alleviated high-fat diet-induced hepatic steatosis[7]. Selegiline hydrochloride (4mg/kg) administered chronically via drinking water to 4-week-old BALB/c mice until 49 weeks of age significantly reduced the progression of age-related hearing loss (ARHL) at high frequencies (8.2 kHz and 16.4 kHz)[8].
References:
[1] Tábi T, Vécsei L, Youdim MB, et al. Selegiline: a molecule with innovative potential. J Neural Transm (Vienna). 2020 May;127(5):831-842.
[2] Gerlach M, Youdim MB, Riederer P. Pharmacology of selegiline. Neurology. 1996 Dec;47(6 Suppl 3):S137-45.
[3] Szczypka M, Sobieszczańska A, Suszko-Pawłowska A, et al. Selegiline and clomipramine effects on lymphocyte subsets, regulatory T cells and sheep red blood cell (SRBC)-induced humoral immune response after in vivo administration in mice. Eur J Pharmacol. 2020 Nov 15;887:173560.
[4] Joung HY, Oh JM, Song MS, et al. Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese Mice. Pharmaceutics. 2023 Oct 27;15(11):2539.
[5] Steib A, Pohóczky K, Tóth N, et al. The MAO-B Inhibitor Selegiline Reduces the Viability of Different Prostate Cancer Cell Lines and Enhances the Effects of Anti-Androgen and Cytostatic Agents. Pharmacol Res Perspect. 2025 Oct;13(5):e70173.
[6] Kumkar PS, Chakraborty R, Upadhyay AM, et al. Preliminary study on cytotoxicity of selegiline on different cancer cell lines: exploration of the induction of ROS-independent apoptosis in breast cancer cells. Med Oncol. 2024 Jul 20;41(8):204.
[7] Tian Z, Wang X, Han T, et al. Selegiline ameliorated dyslipidemia and hepatic steatosis in high-fat diet mice. Int Immunopharmacol. 2023 Apr;117:109901.
[8] Szepesy J, Humli V, Farkas J, et al. Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice. Int J Mol Sci. 2021 Mar 11;22(6):2853.
Selegiline hydrochloride一种选择性单胺氧化酶B抑制剂，用于治疗帕金森病和重度抑郁症[1]。Selegiline hydrochloride可减少多巴胺的降解，从而提高脑内多巴胺的水平[2]。Selegiline hydrochloride还具有多种生物学功能，包括调节脂质代谢、免疫反应等[3-4]。
在体外，Selegiline hydrochloride（100μM–10mM）处理雄激素不敏感（PC-3、DU145）及雄激素敏感（22Rv1、LNCaP、VCaP）前列腺腺癌细胞系48小时，显著降低细胞活力和增殖能力，并增强抗雄激素药物和细胞抑制剂的联合疗效[5]。Selegiline hydrochloride（0–100μg/ml）处理MCF-7乳腺癌细胞、PC12神经元嗜铬细胞瘤细胞及THP-1单核细胞24小时，显著诱导细胞凋亡并抑制细胞增殖，同时降低蛋白激酶C（PKC）的磷酸化水平[6]。
在体内，Selegiline hydrochloride（0.6mg/kg）隔日腹腔注射处理高脂饮食诱导的C57BL/6小鼠6周，显著减轻体重增长、肝脏系数及内脏/皮下脂肪系数，改善血脂异常并降低血清甘油三酯、胆固醇及低密度脂蛋白水平。同时，Selegiline hydrochloride显著缓解高脂饮食诱导的肝脂肪变性[7]。Selegiline hydrochloride（4mg/kg）通过饮用水慢性口服给药处理4周龄BALB/c小鼠直至49周龄，显著减轻年龄相关性听力损失（ARHL）在高频段（8.2 kHz和16.4 kHz）的进展[8]。