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Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs

Abstract

The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist antipsychotics) all of which, despite working by varying mechanisms of actions, act principally on dopamine systems. Many of the second-generation (atypical and dopamine partial agonist) antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the pharmacological properties that confer the different therapeutic effects of the new generation of antipsychotic drugs have remained elusive, and certain side effects can still impact patient health and quality of life. Moreover, the efficacy of antipsychotic drugs is limited prompting the clinical use of adjunctive pharmacy to augment the effects of treatment. In addition, the search for novel and nondopaminergic antipsychotic drugs has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotics, and focuses on novel targets for therapeutic agents for future drug development.

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Acknowledgements

This work was supported in part by the UNC Schizophrenia Research Center, an NIMH Silvio O. Conte Center for the Neuroscience of Mental Disorders (MH064065)(JL), and the Foundation of Hope of Raleigh North Carolina (JL, GD). We thank Mr Kenji Seo and Ms Yoshiko Suzuki for preparing some references. No support was provided by any pharmaceutical company.

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Correspondence to J A Lieberman.

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Miyamoto, S., Duncan, G., Marx, C. et al. Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10, 79–104 (2005). https://doi.org/10.1038/sj.mp.4001556

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  • DOI: https://doi.org/10.1038/sj.mp.4001556

Keywords

  • antipsychotic
  • dopamine partial agonist
  • NMDA receptor
  • metabotropic glutamate receptor
  • schizophrenia

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