The Neurodegenerative Characteristics of Alzheimer’s Disease and Related Multi-Target Drug Design Studies
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Monoamine oxidase (MAO) enzyme activity is one of the critical steps in the control of the function of several neurotransmitters (e.g., serotonin, dopamine, and norepinephrine). In other words, through the formation of aldehyde derivatives of neurotransmitters via MAO catalyzed oxidative deamination reactions, the amine neurotransmitters are deactivated (Shih et al., 1999). There are two types of MAO enzymes in human, as referred to as MAO-A and MAO-B. They display different tissue distribution and ratios depending on age. Although they are capable of employing a diverse amine substrates, there is some selectivity difference. MAO-A shows selectivity for serotonin, melatonin, norepinephrine, and epinephrine, while MAO-B possesses substrate selectivity for benzylamine and phenethylamine. On the other hand, both enzymes display similar characteristics to catalyze dopamine, tyramine, and tryptamine oxidative deamination reactions (Kalgutkar et al., 2001). Depending on the substrate specificity difference, MAO-A inhibition is mainly preferred as an option in the treatment of some form depression (e.g., to increase the available levels of serotonin, norepinephrine, and dopamine) (Meyer et al., 2006). Parkinson disease–related symptoms are generally related to deficiency of dopamine. Regarding the side effects of MAO-A inhibitors, MAO-B inhibitors (e.g., rasagiline, selegiline) are preferred to increase the available amount of dopamine in CNS (Youdim, 2006).
MAO Inhibitors: Predicting Response/Maximizing Efficacy
Mark S. Gold, R. Bruce Lydiard, John S. Carman in Advances in Psychopharmacology: Predicting and Improving Treatment Response, 2018
Monoamine oxidase (MAO) is the enzyme predominantly responsible for intraneuronal metabolism (oxidative deamination) of biogenic amine neurotransmitters. Inhibition of this enzyme increases intracellular stores of these neurotransmitters and is thought to potentiate their action through release of increased amounts into the synaptic cleft. The resulting enhancement of serotonin and norepinephrine activity is shared with the tricyclic antidepressants (TCA) which exert their effects, at least in part, by inhibiting presynaptic reuptake of the neurotransmitters from the synaptic cleft. (This is a bit oversimplified and important secondary receptor actions have also been identified.) While they act in different ways, both classes of drugs provide general support for the monoamine theory of depression and, theoretically, should synergistically enhance one another’s effects1 (see combined MAOI-TCA treatment section).
Antidepressants
Kate McCombe, Lara Wijayasiri, Paul Hatton, David Bogod in The Primary FRCA Structured Oral Examination Study Guide 2, 2017
Mode of action: Prevents breakdown of monoamine neurotransmitters by inhibiting monoamine oxidase (MAO) enzyme.MAOs exist in two isoforms: MAO-A (selectively breaks down serotonin, epinephrine and norepinephrine)MAO-B (selectively breaks down phenethylamine)Both break down dopamine.Older agents inhibit both MAO-A and MAO-B.Newer agents (e.g. moclobemide) selectively inhibit MAO-A and are classed as RIMAs (reversible inhibitors of monoamine oxidase-A).MAO-B inhibitors (e.g. selegiline) are used as anti-Parkinson’s medications due to their dopaminergic properties.
Design of selegiline-loaded bio-nanosuspension for the management of depression using novel bio-retardant from Manilkara zapota
Published in Drug Development and Industrial Pharmacy, 2019
Yogita Tyagi, N. V. Satheesh Madhav
Depression is a common mental illness affecting over 300 million people worldwide and is expected to be a major contributor of the global diseases burden by 2030. The disorder impacts on the family and socioeconomic aspects of patients’ lives as well as imposes a huge financial impact on communities, employers, health care systems, and general government budgets [1]. Monoamine oxidase (MAO) inhibitors had been used for treatment of depression in the late 1950s, and some of them are still prescribed today despite the introduction of new class antidepressants [2]. Selegiline is a preferential MAO-B inhibitor that is currently used as an adjunct therapy to treat late stage Parkinson's disease. Monoamine oxidase is an enzyme which accelerates the breakdown of dopamine. In addition, placebo controlled clinical trials have shown it to have effective antidepressant activity [3–5]. At therapeutic doses up to 10 mg/day orally for PD, selegiline can be safely administered without the need for a tyramine restricted diet. Oral selegiline may be an effective antidepressant [6,7] at doses in excess of 20 mg daily when enzyme selectivity is lost (MAO-A is inhibited in addition to MAO-B), thus necessitating tyramine dietary restrictions [8,9].
Synthesis, in vitro enzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Begüm Nurpelin Sağlık, Derya Osmaniye, Ulviye Acar Çevik, Serkan Levent, Betül Kaya Çavuşoğlu, Özlem Atlı Eklioğlu, Yusuf Özkay, Ali Savaş Koparal, Zafer Asım Kaplancıklı
Monoamine oxidase (MAO) is the enzyme responsible for catalysing the oxidative deamination of intracellular amines and monoamine neurotransmitters, which contributes to the regulation of the concentrations of these chemicals in the brain and in peripheral tissues1,2. MAOs, which are flavin adenine dinucleotide (FAD)-containing enzymes, are localised in the outer mitochondrial membranes of glial, neuronal, and other types of cells; they are particularly abundant in the liver and the brain. MAOs have two different isoforms, MAO-A and MAO-B, with 70% homology. The genes that code for the two isoforms are linked in opposite orientation on the X chromosome, differ in the specificity of their substrates and the selectivity of their inhibitors3. For example, MAO-B is selectively inhibited by selegiline, and utilises phenylethylamine and benzylamine as substrates. On the contrary, MAO-A is selectively inhibited by clorgiline, and utilises adrenaline, noradrenaline and serotonin as substrates. However, both isoforms may also act on the same substrates such as dopamine and tyramine4.
Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I)
Published in Postgraduate Medicine, 2021
Ofelia Loani Elvir-Lazo, Paul F White, Hillenn Cruz Eng, Firuz Yumul, Raissa Chua, Roya Yumul
MAOIs increase the level of amine neurotransmitters (e.g. serotonin and norepinephrine [NE]) by inhibiting monoamine oxidase enzymes, the enzyme normally responsible for the breakdown of these compounds. Monoamine oxidase enzymes can be further classified into MAOIs of type A (MAOA) and type B (MAOB). MOAA targets NE and serotonin, while MAOB targets dopamine and phenylethylamine [94]. Isocarboxazid, tranylcypromine, and phenelzine are MAOIA and B. Commonly used MAOIs include isocarboxazid, phenelzine, tranylcypromine, bifemelane, moclobemide, pirlindole, and selegiline. These drugs are used in psychiatry as antidepressants and/or anti-anxiolytic drugs (to treat social anxiety). Selegiline is a selective MAOIB used for personality and major depressive disorders [95]. Chronic use of these medications may lead to adverse effects on monoamine neurotransmitters (e.g. serotonin, dopamine, NE, and tyramine).
Related Knowledge Centers
- Catalysis
- Enzyme
- Monoamine Neurotransmitter
- Redox
- Mitochondrion
- Protein Family
- Flavin-Containing Amine Oxidoreductase
- Monoamine Oxidase Inhibitor
- Monoamine Oxidase A
- Neuron