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  Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John's wort: An [(11)C]-harmine PET study

Sacher, J., Houle, S., Parkes, J., Rusjan, P., Sagrati, S., Wilson, A. A., et al. (2011). Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John's wort: An [(11)C]-harmine PET study. Journal of Psychiatry & Neuroscience, 36(6), 375-382. doi:10.1503/jpn.100117.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201991/ (Verlagsversion)
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 Urheber:
Sacher, Julia1, 2, 3, 4, 5, Autor           
Houle, Sylvain1, Autor
Parkes, Jun1, Autor
Rusjan, Pablo1, Autor
Sagrati, Sandra1, 2, 3, Autor
Wilson, Alan A.1, Autor
Meyer, Jeffrey H.1, 2, 3, Autor
Affiliations:
1Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, ON, Canada, ou_persistent22              
2Mood and Anxiety Disorders Division, Centre for Addiction and Mental Health, University of Toronto, ON, Canada, ou_persistent22              
3Department of Psychiatry, University of Toronto, ON, Canada, ou_persistent22              
4Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
5Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

Inhalt

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Schlagwörter: Adult; Brain / diagnostic imaging; Brain / drug effects; Brain / enzymology; Carbon Radioisotopes; Depressive Disorder, Major / diagnostic imaging; Depressive Disorder, Major / drug therapy; Depressive Disorder, Major / enzymology; Female; Harmine; Humans; Hypericum; Male; Middle Aged; Moclobemide / pharmacology; Moclobemide / therapeutic use; Monoamine Oxidase / metabolism; Monoamine Oxidase Inhibitors / pharmacology; Monoamine Oxidase; Inhibitors / therapeutic use; Phytotherapy / psychology; Plant Preparations / pharmacology; Plant Preparations / therapeutic use; Positron-Emission Tomography / methods; Positron-Emission Tomography / psychology; Radioligand Assay / methods
 Zusammenfassung: Background

Monoamine oxidase A (MAO-A) inhibitor antidepressants raise levels of multiple monoamines, whereas the selective serotonin reuptake inhibitors (SSRIs) only raise extracellular serotonin. Despite this advantage of MAO-A inhibitors, there is much less frequent development of MAO inhibitors compared with SSRIs. We sought to measure brain MAO-A occupancy after 6 weeks of treatment in depressed patients with a clinically effective dose of a selective MAO-A inhibitor and measure MAO-A occupancy after repeated administration of St. John’s wort, an herb purported to have MAO-A inhibitor properties.
Methods

Participants underwent 2 [11C]-harmine positron emission tomography scans. Healthy controls completed a test–retest condition, and depressed patients were scanned before and after repeated administration of moclobemide or St. John’s wort for 6 weeks at the assigned dose. We measured MAO-A VT, an index of MAO-A density, in the prefrontal, anterior cingulate and anterior temporal cortices, putamen, thalamus, midbrain and hippocampus.
Results

We included 23 participants (10 controls and 13 patients with major depressive disorder [MDD]) in our study. Monoamine oxidase A VT decreased significantly throughout all regions after moclobemide treatment in patients with MDD compared with controls (repeated-measures analysis of variance, F1,15 = 71.08–130.06, p < 0.001 for all regions, mean occupancy 74% [standard deviation 6%]). Treatment with St. John’s wort did not significantly alter MAO-A VT.
Limitations

The occupancy estimates are limited by the sample size of each treatment group; hence, our estimate for the overall moclobemide occupancy of 74% has a 95% confidence interval of 70%–78%, and we can estimate with 95% certainty that the occupancy of St. John’s wort is less than 5%.
Conclusion

For new MAO-A inhibitors, about 74% occupancy at steady-state dosing is desirable. Consistent with this, St. John’s wort should not be classified as an MAO-A inhibitor. The magnitude of MAO-A blockade during moclobemide treatment exceeds the elevation of MAO-A binding during illness by at least 30%, suggesting that the treatment effect should exceed the disease effect when designing selective anti-depressants for this target.

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Sprache(n): eng - English
 Datum: 2011-03-012011-11
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: DOI: 10.1503/jpn.100117
PMID: 21463543
PMC: PMC3201991
 Art des Abschluß: -

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Förderorganisation : Canadian Institutes of Health Research (CIHR)
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Förderorganisation : National Alliance for Research on Schizophrenia and Depression (NARSAD)
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Förderorganisation : Canada Foundation for Innovation (CFI)
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Förderorganisation : Alexander von Humboldt Foundation (AvH)
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Förderorganisation : Ontario Mental Health Foundation (OMHF)
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Förderorganisation : Ontario Ministry of Research and Innovation
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Förderorganisation : GlaxoSmithKline

Quelle 1

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Titel: Journal of Psychiatry & Neuroscience
  Kurztitel : J Psychiatry Neurosci
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: Ottawa, Ont., Canada : Journal of Psychiatry and Neuroscience
Seiten: - Band / Heft: 36 (6) Artikelnummer: - Start- / Endseite: 375 - 382 Identifikator: ISSN: 1180-4882
CoNE: https://pure.mpg.de/cone/journals/resource/1180-4882