Phenelzine is a monoamine oxidase (MAO) inhibitor [1]. Phenelzine irreversibly inhibits monoamine oxidase A and B in the brain, reducing the breakdown of neurotransmitters such as norepinephrine, dopamine, and serotonin, thereby increasing their levels and improving mood [2-3]. Phenelzine is primarily used to treat refractory depression [4].
In PC12 cells, Phenelzine (1-50μM; 24h) reduced the condensation and fragmentation of nuclei caused by 1-methyl-4-phenylpyridinium (MPP+) [5]. In 3T3-F442A and 3T3-L1 cells, reductions in cellular triglycerides and sterol regulatory element binding protein-1c (SREBP-1c) were detected at lower Phenelzine (1-10μM; 8d) concentrations [6]. In Molt-4 cells, Phenelzine (5-25μM; 24h) can upregulate the levels of histone H3K4 monomethylation, H3K4 dimethylation and histone H3 acetylation, upregulate the expression of p21 and p15 proteins, and downregulate the expression of DNMT1, ultimately inhibiting the proliferation of Molt-4 cells and inducing cell apoptosis [7].
In experimental autoimmune encephalomyelitis (EAE) mice model, Phenelzine (15mg/kg; ip; 28d) can delay the onset of disease, alleviate the chronic stage of EAE mice, and significantly improve non-motor symptoms such as exploratory behavior and emotional disorders [8]. In experimental autoimmune encephalomyelitis mice model, Phenelzine (15mg/kg; ip; 14d) elevates the levels of GABA, dopamine and biogenic amines in the central nervous system [9].
References:
[1]. Robinson D S, Nies A, Ravaris C L, et al. The monoamine oxidase inhibitor, phenelzine, in the treatment of depressive-anxiety states: a controlled clinical trial[J]. Archives of General Psychiatry, 1973, 29(3): 407-413.
[2]. Matveychuk D, MacKenzie E M, Kumpula D, et al. Overview of the neuroprotective effects of the MAO-inhibiting antidepressant phenelzine[J]. Cellular and Molecular Neurobiology, 2022, 42(1): 225-242.
[3]. MacKenzie E M, Grant S L, Baker G B, et al. Phenelzine causes an increase in brain ornithine that is prevented by prior monoamine oxidase inhibition[J]. Neurochemical Research, 2008, 33(3): 430-436.
[4]. Van den Eynde V, Abdelmoemin W R, Abraham M M, et al. The prescriber’s guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression[J]. CNS spectrums, 2023, 28(4): 427-440.
[5]. Lee C S, Han E S, Lee W B. Antioxidant effect of phenelzine on MPP+-induced cell viability loss in differentiated PC12 cells[J]. Neurochemical research, 2003, 28(12): 1833-1841.
[6]. Chiche F, Le Guillou M, Chetrite G, et al. Antidepressant phenelzine alters differentiation of cultured human and mouse preadipocytes[J]. Molecular Pharmacology, 2009, 75(5): 1052-1061.
[7]. Qiu Y, Huang Y, Ma X. Effect of phenelzine on the proliferation, apoptosis and histone methylation and acetylation of Molt-4 cells[J]. Zhonghua xue ye xue za zhi= Zhonghua Xueyexue Zazhi, 2016, 37(2): 144-148.
[8]. Musgrave T, Benson C, Wong G, et al. The MAO inhibitor phenelzine improves functional outcomes in mice with experimental autoimmune encephalomyelitis (EAE)[J]. Brain, Behavior, and Immunity, 2011, 25(8): 1677-1688.
[9]. Benson C A, Wong G, Tenorio G, et al. The MAO inhibitor phenelzine can improve functional outcomes in mice with established clinical signs in experimental autoimmune encephalomyelitis (EAE)[J]. Behavioural brain research, 2013, 252: 302-311.
Phenelzine是一种单胺氧化酶（MAO） 抑制剂[1]。Phenelzine不可逆地抑制脑内单胺氧化酶A和B，减少去甲肾上腺素、多巴胺和血清素等神经递质的分解，从而提高这些物质的水平并改善情绪 [2-3]。Phenelzine主要用于治疗难治性抑郁症 [4]。
在PC12细胞中，Phenelzine（1-50μM；24h）可降低1-甲基-4-苯基吡啶（MPP+）引起的细胞核凝聚和碎裂 [5]。在3T3-F442A和3T3-L1细胞中，在较低浓度的Phenelzine（1-10μM；8d）下，可检测到细胞甘油三酯和固醇调节元件结合蛋白-1c（SREBP-1c）的降低 [6]。在Molt-4细胞中，Phenelzine（5-25μM；24h）可以上调组蛋白H3K4单甲基化、H3K4二甲基化和组蛋白H3乙酰化水平，上调p21和p15蛋白表达，下调DNMT1表达，最终抑制Molt-4细胞增殖，诱导细胞凋亡 [7]。
在实验性自身免疫性脑脊髓炎（EAE）小鼠模型中，Phenelzine（15mg/kg；ip；28d）可以延缓发病，缓解EAE小鼠慢性期，并显著改善探索行为、情绪障碍等非运动症状 [8]。在实验性自身免疫性脑脊髓炎小鼠模型中，Phenelzine（15mg/kg；ip；14d）可提高中枢神经系统中GABA、多巴胺和生物胺的水平 [9]。