Skip to main content
SpringerLink
Log in

Neurotransmitter

  • Conference paper
Depression 2000

Zusammenfassung

Ausgangspunkt für die Entwicklung der heutigen Antidepressiva waren die Entdeckung der thymoleptischen Wirkung des trizyklischen Präparates Imipramin im Jahre 1957 und die Beobachtung des stimmungsaufhellenden Effektes des bis dahin in der Tuberkulosebehandlung eingesetzten Monoaminoxidasehemmers (MAO-Hemmers) Iproniazid im selben Jahr. Die sich in den folgenden Jahren anschließenden intensiven pharmakologischen Untersuchungen haben dann in einer Beeinflussung des zentralen Stoffwechsels der Aminneurotransmitter Serotonin und Noradrenalin einen gemeinsamen Wirkungsmechanismus beider Substanzen und ihrer Derivate gezeigt. Da dieser Effekt im Wesentlichen eine initiale Erhöhung der synaptischen Konzentration beider Neurotransmitter beinhaltet, haben diese pharmakologischen Mechanismen zusammen mit einigen zur gleichen Zeit gefundenen pathobiochemischen Veränderungen der noradrenergen bzw. serotoninergen Neurotransmission bei depressiven Patienten zur Formulierung der Noradrenalin-und/oder Serotoninhypothese der Depression geführt (s. Übersicht). Diese ursprünglichen Hypothesen, Verstärkung der noradrenergen und serotoninergen Neurotransmission im ZNS als kausale Therapie eines der Depression zugrunde liegenden Neurotransmittermangels, konnten allerdings in den folgenden 30 Jahren in dieser Einfachheit nicht bestätigt, aber auch nie ganz verworfen werden.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 54.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  • Anand A, Charney DS (2000) Norepinephrine Dysfunction in Depression. J Clin Psychiatry 61 (Suppl 10):16–24.

    PubMed  CAS  Google Scholar 

  • Bartholini G (1985) Gaba receptor agonists: pharmacological spectrum and therapeutic actions. Medical research Reviews 5:55–75.

    Article  CAS  Google Scholar 

  • Chen ACH, Shirayama Y, Shin, KH, Neve RL, Duman RS (2001) Expression of the cAMP response element binding protein (CREB) in hippocampus produces an antidepressant effect. Biol Psychiatry 49:753–762.

    Article  PubMed  CAS  Google Scholar 

  • Dahmen N, Fehr C, Reuß S et al. (1997) Stimulation of immediate early gene expression by desipramine in rat brain. Biol Psychiatry 42:317–323.

    Article  PubMed  CAS  Google Scholar 

  • Delgado PL, Moreno F (1999) Antidepressants and the brain. Intern Clin Psychopharmacology 14 (Suppl 1):9–16.

    Article  Google Scholar 

  • Delgado PL, Moreno FA (2000) Role of norepinephrine in depression. J Clin Psychiatry 61 (Suppl 1):5–12.

    PubMed  CAS  Google Scholar 

  • Delgado PL (2000) Depression: The case for a monoamine deficiency. J Clin Psychiatry 61 (Suppl 6):7–11.

    PubMed  CAS  Google Scholar 

  • Duman RS, Heninger GR, Nestler EJ (1994) Adaptions of receptor-coupled signal transduction pathways underlying stress- and drug-induced neural plasticity. J Nerv Ment Disease 182:692–700.

    Article  CAS  Google Scholar 

  • Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606.

    PubMed  CAS  Google Scholar 

  • Duman RS, Malberg J, Thorne J (1999) Neural plasticity to stress and antidepressant treatment. Biol Psychiatry 46:1181–1191.

    Article  PubMed  CAS  Google Scholar 

  • Duncan GE, Johnson KB, Breese GR (1993) Topographic patterns of brain activity in response to swim stress assessment by 2-deoxyglucose uptake and expression of fos-like immunoreactivity. J Neurosci 13:3932–3934.

    PubMed  CAS  Google Scholar 

  • Francis DD, Caldji C, Champagne F, Plotsky PM, Meaney MJ (1999) The role of corticotropin-releasing factor-norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiatry 46:1153–1166.

    Article  PubMed  CAS  Google Scholar 

  • Frazer, A (2000) Norepinephrine involvement in antidepressant action. J Clin Psychiatry 61 (Suppl 10):25–30.

    PubMed  CAS  Google Scholar 

  • Glassman AH (1998) Cardiovascular effects of antidepressant drugs: updated. J Clin Psychiatry 59 (Suppl 15):13–18.

    PubMed  CAS  Google Scholar 

  • Heninger GR, Delgado L, Charney DS (1996) The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans. Pharmacopsychiatry 29:2–11.

    Article  PubMed  CAS  Google Scholar 

  • Hirschfeld RMA (2000) History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry 61 (Suppl 6):4–6.

    PubMed  CAS  Google Scholar 

  • Hope BT, Kelz M, Duman RS, Nestler EJ (1994) Chronic electroconvulsive seizure (ECS) treatment results in expression of a long-lasting AP-1 complex in brain with altered composition and characteristics. J Neurosci 14:4318–4328.

    PubMed  CAS  Google Scholar 

  • Hudson CJ, Young LT, Li PP, Warsh JJ (1993) CNS signal transduction in the pathophysiology and pharmacotherapy of affective disorders and schizophrenia. Synapse 13:278–293.

    Article  PubMed  CAS  Google Scholar 

  • Johnston TG, Kelly CB, Stevenson MR, Cooper SJ (1999) Plasma norepinephrine and pre-diction of outcome in major depressive disorder. Biol Psychiatry 46:1253–1258.

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (1999) Corticotroptin-releasing factor, norepinephrine, and stress. Biol Psychiatry 46:1167–1180.

    Article  PubMed  CAS  Google Scholar 

  • Lambert G, Johansson M, Ågren H, Friberg P (2000) Reduced brain norepinephrine and dopamine release in treatment-refactory depressive illness. Arch Gen Psychiatry 57:787–793.

    Article  PubMed  CAS  Google Scholar 

  • Lenox RH, Hahn CG (2000) Overview of the mechanism of action of lithium in the brain: fity-year update. J Clin Psychiatry 61 (Suppl 9):5–15.

    PubMed  CAS  Google Scholar 

  • Leonard BE (2000) Evidence for a biochemical lesion in depression. J Clin Psychiatry 61 (Suppl 6):12–17.

    PubMed  CAS  Google Scholar 

  • Manji HK, Moore GJ, Chen G (2000) Lithium up-regulates the cytoprotective protein bcl-2 in the CNS in vitro: a role for neurotrophic and neuroprotective effects in manic depressive illness. J Clin Psychiatry 61 (Suppl 9):82–96.

    PubMed  CAS  Google Scholar 

  • Möller HJ, Müller WE, Volz HP (Hrsg) (2000) Psychopharmakotherapie, 2. Aufl. Ein Leitfaden für Klinik und Praxis. Kohlhammer, Stuttgart.

    Google Scholar 

  • Morinobu S, Nibuya M, Duman RS (1995) Chronic antidepressant treatment down-regulates the induction of c-fos mRNA in response to acute stress in rat frontal cortex. Neuropschychopharmacology 12:221–228.

    Article  CAS  Google Scholar 

  • Müller WE, Eckert A (1997) Pharmakodynamische Grundlagen der Therapie mit spezifischen Serotonin-Wiederaufnahmehemmern. Psychopharmakotherapie 4 (Suppl 7):2–8.

    Google Scholar 

  • Müller WE (1999) Pharmakologische Grundlagen der Therapie mit Neuroleptika außerhalb ihrer Anwendung bei Schizophrenen. In: Gaebel W, Klimke A (Hrsg) Neuroleptika bei nichtpsychotischen Störungen. Grundlagen und Indikationen. Springer, Berlin Heidelberg New York Tokyo, S 15–30.

    Google Scholar 

  • Müller WE, Singer A, Wonnemann M (1999) Johanniskraut. Vom Nerventee zum modernen Antidepressivum. Deutsche Apothekerzeitung 139:1741–1750.

    Google Scholar 

  • Müller, WE (2000) Neue Antidepressiva. Mehr Licht in das Dunkel der Seele. Pharmazeutische Zeitung 145:1765–1772.

    Google Scholar 

  • Müller WE, Eckert A (2000) Psychopharmakotherapie: pharmakologische Grundlagen. In: Möller HJ, Laux G, Kapfhammer HP (Hrsg) Psychiatrie und Psychotherapie. Springer, Berlin Heidelberg New York Tokyo, S 498–542.

    Google Scholar 

  • Murphy DL, Andrews, AM, Wichems CH, Li Q, Tohda M, Greenberg B (1998) Brain serotonin neurotransmission: an overview and update with an emphasis on seretonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs. J Clin Psychiatry 59 (Suppl 15):4–12.

    PubMed  CAS  Google Scholar 

  • Nelson JC (1999) A review of the efficacy of serotonergic and noradrenergic reuptake inhibitors for treatment of major depression. Biol Psychiatry 46:1301–1308.

    Article  PubMed  CAS  Google Scholar 

  • Racagni G, Brunello N, Tinelli D, Perez J (1992) New biochemical hypotheses on the mechanism of action of antidepressant drugs: cAMP — dependent phosphorylation system. Pharmacopsychiatry 25:51–55.

    Article  PubMed  CAS  Google Scholar 

  • Rajkowska G, Miguel-Hidalgo JJ, Wei J et al. (1999) Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 45:1085–1098.

    Article  PubMed  CAS  Google Scholar 

  • Ressler KJ, Nemeroff CB (1999) Role of norepinephrine in the pathophysiology and treatment of mood disorders. Biol Psychiatry 46:1219–1233.

    Article  PubMed  CAS  Google Scholar 

  • Riedel M, Müller N, Müller WE, Möller, HJ (2000) Nefazodon, ein dual-serotonerges Anti-depressivum. Psychopharmakotherapie 7:117–124.

    Google Scholar 

  • Sapolsky RM, Krey LC, McEwen BS, (1985) Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neuro Sci 5:1222–1227.

    CAS  Google Scholar 

  • Skolnick P, Legutko B, Li X, Bymaster FP (2001) Current perspektives on the development of non-biogenic amine-based antidepressants. Pharmacol Resarch 43:411–422.

    Article  CAS  Google Scholar 

  • Soares JC, Mann JJ (1997) The anatomy of mood disorders — review of structural neuroimaging studies. Biol Psychiatry 41:86–106.

    Article  PubMed  CAS  Google Scholar 

  • Stassen HH, Angst J, Delini-Stula A (1996) Delayed onset action of antidepressant drugs? Survey of results of Zurich meta-analyses. Pharmacopsychiatry 29:87–96.

    Article  PubMed  CAS  Google Scholar 

  • Stone EA, Quartermain D (1999) Alpha-1-noradrenergic neurotransmission, corticosterone, and behavioral depression. Biol Psychiatry 46:1287–1300.

    Article  PubMed  CAS  Google Scholar 

  • Vaidya VA, Siuciak J, Du F, Duman RS (1999) Mossy fiber sprouting and synaptic reorganization induced by chronic administration of electroconvulsive seizure: role of BDNF. Neuroscience 89:157–166.

    Article  PubMed  CAS  Google Scholar 

  • Velbinger K, de Vry J, Jentzsch K, Eckert A, Henn F, Müller WE (2000) Acute stress induced modifications of calcium signalling in learned helpess rats. Pharmacopsychiatry 33: 132–137.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe Y, Gould E, Daniels DC, Cameron H, McEwen BS (1992) Tianeptine attenuates stress-induced morphological changes in the hippocampus. Eur J Pharmacol 222:157–162.

    Article  PubMed  CAS  Google Scholar 

  • Wilde MI, Benfield P (1995) Tianeptine. A review of its pharmacodynamic and pharmakokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression. Drugs 49:411–439.

    Article  PubMed  CAS  Google Scholar 

  • Winston SM, Hayward MD, Nestler EJ, Duman RS (1990) Chronic electroconvulsive seizures down-regulate expression of the immediate-early genes c-fos and c-jun proto-oncogenes in rat cerebral cortex. J Neurochem 54:1920–1925.

    Article  PubMed  CAS  Google Scholar 

  • Zhu MY, Klimek V, Dilley GE, Haycock JW, Stockmeier C, Overholser JC, Meltzer HY, Ordway GA (1999) Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression. Biol Psychiatry 46:1275–1286.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. W. E. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Fachkrankenhaus für Psychiatrie, Psychotherapie und Neurologie, Bezirksklinikum Gabersee, Gabersee 7, 83512, Wasserburg am Inn, Germany

    G. Laux

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Müller, W.E. (2002). Neurotransmitter. In: Laux, G. (eds) Depression 2000. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59394-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-59394-9_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63963-0

  • Online ISBN: 978-3-642-59394-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation