A neuroscientific update on monoamine oxidase and its inhibitors

Abstract

The goal of this brief review is to explain the role of monoamine oxidase enzymes in the neurobiology, etiology, and presentation of psychiatric illnesses, primarily major depressive disorder. This article will initially focus on the basic science and function of the monoamine oxidase system and some proposed neuropsychiatric symptoms that may arise if this enzyme system is altered by genetic predisposition. These findings and theories will next be translationally discussed in regard to clinical application pertaining to enzyme inhibition and the treatment of major depressive and other psychiatric disorders.

Azure B and a synthetic structural analogue of methylene blue, ethylthioninium chloride, present with antidepressant-like properties

“…Another major disadvantage of MAO-A inhibitors and possibly MB is the concern for development of hypertensive crisis due to the interaction of inhibitors of MAO-A with tyramine and other monoamine releasing compounds (Brown et al, 1989). Despite these concerns, there remains a growing interest in the clinical benefit and utility of MAO-inhibitors in the treatment of depression (Schwartz, 2013;Lum and Stahl, 2012). In this study we propose to synthesise a derivative of MB and to characterize its interactions with recombinant human MAO-A and MAO-B.…”

Monoamine oxidase‐B inhibitors as potential neurotherapeutic agents: An overview and update

“…Moreover, trace monoamines such as tryptamine and octopamine are also increased after MAO inhibition . Since the deficiencies of these two neurotransmitters are linked to the development of depression, MAO‐AIs have been extensively used as antidepressant agents . The antidepressant efficacy of MAO‐AIs may be due to the increase in the intrasynaptic concentration of monoamines and reduction in the levels of corresponding deaminated metabolites.…”

“…38 Since the deficiencies of these two neurotransmitters are linked to the development of depression, MAO-AIs have been extensively used as antidepressant agents. 39,40 The antidepressant efficacy of MAO-AIs may be due to the increase in the intrasynaptic concentration of monoamines and reduction in the levels of corresponding deaminated metabolites. Mild retardation and prominent behavioral abnormalities in males 41 and aggressive behavior in mice 42 have been observed in case of loss of MAO-A function.…”

“…Chromane-2,4-diones (37a-d) and chromone-3-carboxamides (38a-d) 170. hMAO, human monoamine oxidase; IC50 , half maximal inhibitory concentration; SI, selectivity index TRIPATHI AND AYYANNAN |1629 Kallitsakis et al171 investigated purine + coumarin hybrids(39)(40)(41)(42) for the MAO-B inhibitory activity (Figure 31).The hybrids were selective MAO-BIs, the most potent being 40 (IC 50 = 6.8 ± 0.6 μM; SI > 14.7). However, the compound was found to be much less potent than L-deprenyl (IC50 = 17.3 ± 1.9 nM) for MAO-B.…”

Monoamine oxidase A (MAO-A): a signature marker of alternatively activated monocytes/macrophages

“…This enzyme reaction requires molecular dioxygen and generates stoichiometric amounts of hydrogen peroxide and ammonia [18, 19] . MAO-A hyperactivity has been shown to be associated with depression and previous reports implicate MAO-A inhibitors as effective therapeutics against clinical depression and anxiety [20, 21] . Previous studies also demonstrated the involvement of MAO-A in neurodegeneration including Parkinson's and Alzheimer's diseases by inducing oxidative stress-mediated apoptosis [22, 23] .…”