Schizophrenia: a review of neuropharmacology

  • J. Lyne
  • B. D. KellyEmail author
  • W. T. O’ Connor



The last few decades have seen significant advances in our understanding of the neurochemical basis of schizophrenia.


To describe the neurotransmitter systems and nerve circuits implicated in schizophrenia; to compare the neuropharmacology of typical and atypical anti-psychotic agents; and to describe recent developments in the pharmacological treatment of schizophrenia.


Relevant pharmacological, neurophysiological and psychiatric literature was examined and reviewed.


Schizophrenia is associated with abnormalities of multiple neurotransmitter systems, including dopamine, serotonin, gamma-aminobutyric acid and glutamate. Typical and atypical antipsychotic agents differ in their receptorbinding affinities, which are related to their differing side-effect profiles. Novel therapeutic strategies include normalisation of synaptic dopamine or serotonin levels, serotonin receptor antagonism and modulation of cerebral protein synthesis.


The ideal treatment for schizophrenia may not be a single pharmacological agent but several agents that match the different expressions of the illness, in combination with psycho-social interventions.


Schizophrenia Clozapine Olanzapine Quetiapine Ventral Tegmental Area 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Torrey EF. Prevalence studies in schizophrenia.Br J Psychiatry 1987; 150: 598–608.CrossRefPubMedGoogle Scholar
  2. 2.
    Jablensky A. The 100-year epidemiology of schizophrenia.Schizophr Res 1997; 28: 111–28.CrossRefPubMedGoogle Scholar
  3. 3.
    Daly A, Walsh D. Irish Psychiatric Services: Activities 2000. Dublin: Health Research Board, 2001.Google Scholar
  4. 4.
    Kahn, Rene S, Davis Kenneth L. New Developments in Dopamine and Schizophrenia. The American College Of Neuropsychopharmacology 2000.Google Scholar
  5. 5.
    Gelder M, Gath D, Mayou R, Cowen P. Oxford Textbook of Psychiatry (3rd edition), Oxford University Press, Oxford 1996.Google Scholar
  6. 6.
    Abi-Dargham A, Guo NN, Lombardo I et al. Selective Upregulation Of Prefrontal D1 Receptors In Schizophrenia Predicts Poor Working Memory Performance. NeuroReceptor Mapping 2002 Meeting. Elsevier Science, New York 2002.Google Scholar
  7. 7.
    Rang HP, Dale MM, Ritter JM et al. Pharmacology. Churchill Livingstone, New York 1999.Google Scholar
  8. 8.
    Roth BL, Meltzer HY. The role of serotonin in schizophrenia. The American College Of Neuropsychopharmacology, New York 2000.Google Scholar
  9. 9.
    Roth BL, Hanizavareh SM, Blum AE. Serotonin receptors represent highly favourable molecular targets for cognitive enhancement in schizophrenia and other disorders.Psychopharmacol (Berl) 2004; 174: 17–24.Google Scholar
  10. 10.
    Fan JB, Sklar P. Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia.Mol Psychiatry 2004 Aug 31 [Epub ahead of print] (available at Scholar
  11. 11.
    Goodman LS, Gilman A. The Pharmacological Basis of Therapeutics, McGraw Hill, New York 1996.Google Scholar
  12. 12.
    Kaplan VA, Sadcock BJ. Comprehensive Textbook of Psychiatry. Lippencott Williams & Wilkins, New York 1995.Google Scholar
  13. 13.
    Gluck MR, Thomas RG, Davis KL, Haroutunian V. Implications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients.Am J Psychiatry 2002; 159: 1165–73.CrossRefPubMedGoogle Scholar
  14. 14.
    Berretta S, Munno DW, Benes FM. Amygdalar activation alters the hippocampal GABA system: “partial” modelling for postmortem changes in schizophrenia.J Comp Neurol 2001; 431: 129–38.CrossRefPubMedGoogle Scholar
  15. 15.
    O’Connor WT. Functional neuroanatomy of the ventral striopallidal GABA pathway. New sites of intervention in the treatment of schizophrenia.J Neurosci Methods 2001; 109: 31–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Diaz-Cabiale Z, Vivo M, Del Arco A et al. Metabotropic glutamate mGlu5 receptor-mediated modulation of the ventral striopallidal GABA pathway in rats. Interactions with adenosine A(2A) and dopamine D(2) receptors.Neurosci Lett 2002; 324: 154–8.CrossRefPubMedGoogle Scholar
  17. 17.
    O’Connor WT. Functional neuroanatomy of the basal ganglia as studied by dual-probe microdialysis.Nucl Med Biol 1998; 25: 743–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Fendt M. Enhancement of prepulse inhibition after blockade of GABA activity within the superior colliculus. Brain Res 1999; 833: 81–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Fendt M, Schwienbacher I, Koch M. Amygdaloid N-methyl-D-aspartate and gamma-aminobutyric acid(A) receptors regulate sensorimotor gating in a dopamine-dependent way in rats.Neuroscience 2000; 98: 55–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Bunney G. B., Bunney Jr., W.E., Carlsson A. Schizophrenia and Glutamate: An update. The American College Of Neuropsychopharmacology, New York 2000.Google Scholar
  21. 21.
    McEvoy JP, Scheifler Pl, Frances A. Expert consensus guideline series. Treatment of schizophrenia.J Clin Psychiatry 1999; 60 Suppl 11: 3–80.Google Scholar
  22. 22.
    Seeman P. Atypical antipsychotics: mechanism of action.Can J Psychiatry 2002; 47: 27–38.PubMedGoogle Scholar
  23. 23.
    Meltzer HY. Atypical antipsychotic drugs. The American College Of Neuropsychopharrnacology, New York 2000.Google Scholar
  24. 24.
    Wadenberg ML, Soliman A, VanderSpek SC et al. Dopamine D(2) receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effects.Neuropsychopharmacol 2001; 25: 633–41.CrossRefGoogle Scholar
  25. 25.
    Tamminga CA. Partial dopamine agonists in the treatment of psychosis.J Neural Transm 2002; 109: 411–20.CrossRefPubMedGoogle Scholar
  26. 26.
    Lieberman JA. Dopamine partial agonists: a new class of antipsychotic.CNS Drugs 2004; 18: 251–67.CrossRefPubMedGoogle Scholar
  27. 27.
    Moises Hans WM. Human Genome data analyzed by an evolutionary method suggests a decrease in cerebral protein-synthesis rate as cause of schizophrenia and an increase as antipsychotic mechanism.BioMed Central Psychiatry 2002; 2: 8 (available at Scholar
  28. 28.
    Albert KA, Hemmings HC Jr, Adamo AI et al. Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia.Arch Gen Psychiatry 2002; 59: 705–12.CrossRefPubMedGoogle Scholar
  29. 29.
    Kapur S, Remington G. Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient.Biol Psychiatry 2001; 50: 873–83.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2004

Authors and Affiliations

  1. 1.Department of Psychiatry and Mental Health ResearchSt Vincent’s University Hospital/University College DublinDublin
  2. 2.Stanley Research Unit, Department of Adult PsychiatryHospitaller Order of St John of God, Cluain Mhuire Family CentreBlackrock
  3. 3.Department of Human Anatomy and Physiology, National Neuroscience Network, The Conway InstituteUniversity College DublinIreland

Personalised recommendations