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β-Carbolines and Neuroprotection: Inhibition of Monoamine Oxidase

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Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 1))

Abstract

Recent studies with MAO B inhibitors do not support the notion of neuroprotective actions by direct inhibition of the isoenzyme nor by inhibition of MAO A. MAO activity is present in the brain in large amounts. MAO B is increased in Parkinson’s disease (PD) due to gliosis and in smokers by a compensatory mechanism for the inhibition of the enzyme by compounds contained in tobacco smoke. Both isoenzymes should be inhibited to a certain extent to achieve neuroprotection by decreasing the production of detrimental reactive oxygen species (ROS). The correlation between the levels of the βCs norharman (inhibitor of MAO B) and harman (inhibitor of MAO A) in tobacco smoke and the proportion of the inhibited isoenzymes in the human brain measured by PET strongly support the notion that these two βCs are responsible for the inhibition of MAO A and B in human brain from smokers. Epidemiologic studies show that smoking subjects have a reduced risk for developing PD. Studies using in vivo microdialysis and electrophysiology demonstrate a preference of the βCs for dopamine neurons. Provided smoking a full cigarette results in more than 88% nicotinic receptor occupancy associated with desensitization of these receptors, we postulate that the βCs contribute substantially not only to the neuroprotective actions of smoke with a reduced risk for PD but also to the addictive effects specifically to improve mood and pleasure.

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Authors and Affiliations

  1. Department of Psychiatry, Charité-University Medicine, Campus Benjamin Franklin, Charitéplatz 1, 10117, Berlin, Germany

    Hans Rommelspacher

  2. Department of Psychiatry, Charité-University Medicine, Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany

    Hans Rommelspacher

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  1. Hans Rommelspacher
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Correspondence to Hans Rommelspacher .

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  1. Smetna 12, Krakow, 31-343, Poland

    Lucyna Antkiewicz-Michaluk

  2. , Departments of Psychiatry, Charité-University Medicine, Berlin, 10117, Germany

    Hans Rommelspacher

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Rommelspacher, H. (2012). β-Carbolines and Neuroprotection: Inhibition of Monoamine Oxidase. In: Antkiewicz-Michaluk, L., Rommelspacher, H. (eds) Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants. Current Topics in Neurotoxicity, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1542-8_7

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