title: Use of monoamine oxidase inhibitors in chronic neurodegeneration.
abstract: Neurotransmission by biogenic monoamines is important for brain function. Biogenic amine turnover employs the enzymes catechol-O-methyltransferase and monoamine oxidase in neuronal and glial cells. Inhibition of these enzymes elevates biogenic amine levels in the synaptic cleft. Subtype selectivity of inhibition is lost during long-term use of 'selective' monoamine oxidase inhibitors. Areas covered: This narrative review discusses use of monoamine oxidase inhibitors in the context with chronic neurodegeneration. Expert opinion: Antidepressant drugs increase synaptic concentrations of biogenic amines. In the aging brain, then one of the two enzymes involved in degrading synaptic amines, catechol-O-methyl transferase, increasingly catalyzes methylation processes. Therefore, metabolism by monoamine oxidase plays an incremental, predominant role in biogenic amine turnover, leading to greater oxidative stress. In patients with chronic neurodegenerative disorders, symptoms, such as depression and apathy, are often treated with drugs that elevate biogenic amine levels. This therapeutic strategy increases biogenic amine turnover, thereby generating neurotoxic aldehydes and enhanced oxidative stress, each of which influence and accelerate the course of neurodegeneration. We propose that antidepressant therapy should be initiated first with monoamine oxidase inhibitors only. If adequate clinical response is not achieved, only then they should be supplemented with a further antidepressant.
authors.affiliation: a Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy , University Hospital Würzburg , Würzburg , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.affiliation: b Department of Neurology , St. Joseph Hospital Berlin-Weißensee , Berlin , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001679:Biogenic Amines / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002908:Chronic Disease; D006801:Humans; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D001679:Biogenic Amines; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase
keywords: DOPAL; Monoamine oxidase; antidepressants; depression; moclobemide; oxidative stress; rasagiline; selegiline