Schizophrenie pp 185-197 | Cite as

Antipsychotische Wirkungsmechanismen der Neuroleptika bei Schizophrenie: Spekulative Betrachtungen

  • C. A. Tamminga
  • R. A. Lahti
Conference paper

Zusammenfassung

Neuroleptika stehen seit Mitte der 60er Jahre als antipsychotisch wirksame Substanzen zur Behandlung der Schizophrenie sowie von psychotisch-affektiven Störungen und anderen Psychosen zur Verfügung. Sie besitzen eine klinisch vielfach bestätigte, spezifische und zuverlässige Wirkung gegen Halluzinationen, Denkstörungen, Wahnvorstellungen und paranoide Zustände (Klein u. Davis 1969). Seit der ursprünglichen Entdeckung von Chlorpromazin (Delay et al. 1952) und der Hypothese seines Wirkungsmechanismus auf der Ebene des Dopaminrezeptors (Carlsson u. Lindqvist 1963; Sedvall 1990) ist eine Fülle antipsychotisch wirksamer Substanzen in die Therapie eingeführt worden. Sie besitzen zwar unterschiedliche neurochemische Eigenschaften (Hyttel et al. 1985), gemeinsam ist ihnen jedoch der Antagonismus gegenüber der Gruppe der D2-Rezeptoren. Creese et al. (1976) haben gezeigt, daß die Affinität der Neuroleptika zu D2-Rezeptoren eng mit ihrer klinischen Wirksamkeit korreliert. Heute, nachdem mehrere Untergruppen von D2-Rezeptoren bekannt sind, die möglicherweise alle ihre eigenen Aktivitätsprofile aufweisen, ergibt sich die Notwendigkeit, die Bedeutung der D2-Rezeptorsubtypen für die Schizophrenie genauer zu hinterfragen. Den traditionellen Neuroleptika schreibt man eine klinisch weitgehend gleichwertige antipsychotische Wirkung, jedoch unterschiedliche Nebenwirkungsprofile zu. Neue Neuroleptika scheinen dagegen ein breiteres antipsychotisches Profil und geringere Nebenwirkungen zu besitzen (Tamminga u. Gerlach 1987).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segre-gated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9: 357–381PubMedCrossRefGoogle Scholar
  2. Benes FM, Bird ED (1987) An analysis of the arrangement of neurons in the cingulate cor-tex of schizophrenic patients. Arch Gen Psychiatry 44: 608–616PubMedGoogle Scholar
  3. Bogerts B, Meertz E, Schonfeldt-Bausch R (1985) Basal ganglia and schizophrenia. Arch Gen Psychiatry 43: 784–791Google Scholar
  4. Buchsbaum MS, Wu JC, DeLisi LE, Holcomb HH, Hazlett E, Copper-Langston K, Kessler R (1987) Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: Differences between normal control and schizophrenic patients. Biol Psychiatry 22: 479–494PubMedCrossRefGoogle Scholar
  5. Carlsson A, Lindqvist M (1963) Effect of chlorpromazine and haloperidol on the formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol (Copenhagen) 20: 140–144CrossRefGoogle Scholar
  6. Carlsson M, Carlsson A (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia — implications for schizophrenia and Parkinson’s disease. TINS 13: 272–276PubMedGoogle Scholar
  7. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192: 481–483PubMedCrossRefGoogle Scholar
  8. Delay J, Deniker P, Harl JM (1952) Traitement des états d’excitation et d’agitation par une méthode médicamenteuse dérivée de l’hibernothérapie. Ann Méd Psychol 10: 267–273Google Scholar
  9. Graybiel AM (1990) Neurotransmitters and neuromodulators in the basal ganglia. Trends in Neurosciences 7: 244–254CrossRefGoogle Scholar
  10. Heimer L, Wilson RD (1975) The subcortical projections of the allocortex: Similarities in the neural associations of the hippocampus, the piriform cortex, and the neocortex. In: Santini Golgi Centennial Symp, Raven, New York, pp 177–193Google Scholar
  11. Holcomb HH, Tamminga CA, Cascella NG et al (1994) Functional sites of neuroleptic drug action in human brain: PET/FDG studies with and without haloperidol. Arch Gen Psychiatry (im Druck )Google Scholar
  12. Hyttel J, Lanen JJ, Christensen AV, Amt J (1985) Characterization of antipsychotic drugs using biochemistry and behavior. In: Casey DE, Chase TN (eds) Dyskinesia research and treatment. Springer, Berlin Heidelberg New York, pp 9–18CrossRefGoogle Scholar
  13. Jakob H, Beckman H (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 65: 303–326PubMedCrossRefGoogle Scholar
  14. Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 45: 789–796PubMedGoogle Scholar
  15. Klein DF, Davis JM (1969) Review of antipsychotic drug literature. In: Klein DF, Davis JM (eds) Diagnosis and drug treatment of psychiatric disorders. William & Wilkins, Baltimore, MD, pp 52–138Google Scholar
  16. Kornhuber HH, Kornhuber J, Kim JS, Kornhuber ME (1984) Zur biochemischen Theorie der Schizophrenie. Nervenarzt 55: 602–606PubMedGoogle Scholar
  17. Kozlowski MR, Marshall JF (1980) Plasticity of 14C-Deoxy-d-glucose incorporation into neostriatum and related structures in response to dopamine neuronal damage and apomorphine replacement. Brain Res 197: 167–183PubMedCrossRefGoogle Scholar
  18. Martin P, Carlsson ML, Carlsson A (1993) GABA accumulation in mouse thalamus following GABA-T inhibition; effects of dopaminergic manipulations. Neurosci Abst 19: 782Google Scholar
  19. Nauta WJH (1989) Reciprocal links of the corpus striatum with the cerebral cortex and limbic system: A common substrate for movement and thought? In: Mueller (ed) Neurology and psychiatry: A meeting of minds. Karger, Basel, pp 43–63Google Scholar
  20. Pakkenberg B (1990) Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 47: 1023–1027PubMedGoogle Scholar
  21. Resnick SM, Gur RE, Alavi A, Gur RC, Reivich M (1988) Positron emission tomography and subcortical glucose metabolism in schizophrenia. Psychiatry Res 24: 1–11PubMedCrossRefGoogle Scholar
  22. Scheibel AB, Kovelman JA (1981) Disorientation of the hippocampal pyramidal cell and its processes in schizophrenia patients. Biol Psychiatry 16: 101–102Google Scholar
  23. Sedvall G (1990) PET imaging of dopamine receptors in human basal ganglia: Relevance to mental illness. Trends in Neuroscience 13: 302–308CrossRefGoogle Scholar
  24. Seeman P (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1: 133–152PubMedCrossRefGoogle Scholar
  25. Seeman P, Guan HC, Van Tol HHM (1993) Dopamine D4 receptors elevated in schizophrenia. Letters to Nature 365: 441–445CrossRefGoogle Scholar
  26. Stevens JR (1973) An anatomy of schizophrenia? Arch Gen Psychiatry 29: 177–189PubMedGoogle Scholar
  27. Suddath RL, Casanova MF, Goldberg TE (1989) Temporal lobe pathology in schizophre-nia: A quantitative magnetic resonance imaging study. Am J Psychiatry 146: 464–472PubMedGoogle Scholar
  28. Tamminga CA, Gerlach J (1987) New neuroleptics and experimental antipsychotics in schizophrenia. In: Meltzer HY (Hrsg) Psychopharmacology: The third generation of progress. Raven, New York, NY, pp 1129–1140Google Scholar
  29. Tamminga CA, Lahti AC, Gao X-M (im Druck) Schizophrenic psychosis: Speculative new evidence to support the glutamatergic hypothesis of pathophysiology. In: Moroji M (ed) Schizophrenia research. Elsevier, New YorkGoogle Scholar
  30. Tamminga CA, Shirakawa O, Conley RR (1993) Nontarget actions of neuroleptics. In: Brunello N, Mendlewicz J, Racagni G (eds) New generation of antipsychotic drugs: Novel mechanisms of action. Int Acad Biomed Drug Res. Karger, Basel, Vol 4, pp 67–76Google Scholar
  31. Tamminga CA, Thaker GK, Buchanan R, Kirkpatrick B, Alphs LD, Chase TN, Carpenter WT (1992) Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Arch Gen Psychiatry 49: 522–530PubMedGoogle Scholar
  32. Teuber HL (1976) Complex functions of the basal ganglia: In: Yahr M (ed) Basal ganglia. Raven, New YorkGoogle Scholar
  33. Volkow ND, Brodie JD, Wolf AP, Angrist B, Russell J, Cancro R (1986) Brain metabolism in patients with schizophrenia before and after acute neuroleptic administration. J Neural Neurosurg Psychiatry 49: 1199–1202CrossRefGoogle Scholar
  34. Weinberger DR, Berman KF, Zee RF (1986) Physiologic dysfunction of dorso-lateral prefrontal cortex in schizophrenia. I: Regional cerebral blood flow evidence. Arch Gen Psychiatry 43: 114–124PubMedGoogle Scholar
  35. Wong DF, Wagner HN Jr, Tobe LE et al. (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234: 1558–1563PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • C. A. Tamminga
  • R. A. Lahti

There are no affiliations available

Personalised recommendations