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.