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Dopamine Receptors and the Treatment of Schizophrenia

Part of the The Receptors book series (REC)

Abstract

Schizophrenia is a most disabling psychiatric disorder characterized by a myriad of symptoms. While the delusions and hallucinations are the most iconic symptoms of schizophrenia, patients also exhibit negative and cognitive symptoms. It is thought that these symptoms arise, at least in part, through a cortical–subcortical imbalance of dopamine function and pharmacological approaches that reduce dopaminergic neurotransmission through dopamine receptor blockade, and in particular through the D2 receptor, have antipsychotic action in humans. However, D2 antagonists are not optimally effective against the full spectrum of schizophrenia symptoms and induce side effects that limit their use. Research to enhance the therapeutic benefits of antipsychotics while diminishing their side effects has led to the development of atypical antipsychotics (D2 antagonists with activity at other receptors) and, more recently, a new strategy using dopamine partial agonists to reduce dopaminergic neurotransmission has proven to be successful. This chapter reviews the pharmacological effects of typical and atypical antipsychotics on the different dopamine receptor subtypes, as well as on non-dopaminergic receptor targets, and on the prominent role of D2 receptor blockade as the primary site of their action in brain. In addition, we discuss current theories on the mechanisms of antipsychotic action, including the role of combined action at the dopamine and serotonin receptors, transient dopamine D2 blockade, preferential blockade of limbic D2 receptors, or combined blockade of D1 and D2 receptors. Some critical clinical considerations with regard to the speed of onset action and the occurrence of relapse and supersensitivity psychosis on withdrawal are discussed with special relevance to their relationship to the dopamine system. While the D2 receptor-based treatments seem to have dominated the field till now, drugs that reduce dopamine-mediated transmission through action at presynaptic sites and of drugs providing D1 signaling augmentation in prefrontal cortex may provide novel therapeutic avenues for the treatment of schizophrenia.

Keywords

  • Schizophrenia
  • Antipsychotic action
  • Dopamine receptor blockade
  • D2 antagonist
  • D2 partial agonist
  • D2 inverse agonist
  • Relapse
  • Supersensitivity
  • Tardive dyskinesia

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Ginovart, N., Kapur, S. (2010). Dopamine Receptors and the Treatment of Schizophrenia. In: Neve, K. (eds) The Dopamine Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-333-6_16

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