Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial

@article{Corrigan2004EffectivenessOT,
  title={Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial},
  author={Mark H. Corrigan and Christopher C. Gallen and Maria Luisa Bonura and Kalpana Merchant},
  journal={Biological Psychiatry},
  year={2004},
  volume={55},
  pages={445-451}
}

Role of dopamine D(2) receptors for antipsychotic activity.

TLDR
This review summarizes the current state of knowledge and presents some critical clinical considerations regarding the mechanisms linking dopamine disturbance to the expression of psychosis and its blockade to the progressive resolution of psychosis, keeping in perspective the speed and onset of antipsychotic action.

Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents

TLDR
An update and critical review of the pharmacology and clinical profiles of current antipsychotic drugs and drugs acting on novel targets with potential to be therapeutic agents in the future is provided.

Experimental studies on novel pharmacological strategies in the treatment of schizophrenia

TLDR
Investigating the effects of adjunctive treatment with either a low dose of L-dopa or topiramate to low doses of the selective DA D2 receptor antagonist raclopride using the conditioned avoidance response (CAR) paradigm concluded that an enhanced prefrontal DA output per se may serve to improve the effect of typical APDs in schizophrenia.

Dopamine Receptors and the Treatment of Schizophrenia

TLDR
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.

Strategies for pharmacotherapy of schizophrenia

TLDR
Various strategies to improve cortical function are described, which is believed to be suboptimal in patients with cognitive deficits and negative symptoms, which include drug actions on dopamine, 5-HT, norepinephrine, nicotinic and muscarinic receptor subtypes, as well as various glutamatergic drug targets.

Drugs in development for the treatment of schizophrenia

  • R. Emsley
  • Psychology, Medicine
    Expert opinion on investigational drugs
  • 2009
TLDR
An up-to-date review of antipsychotic drugs currently in development, focusing on the findings to date for compounds that are presently in Phase III clinical trials, suggests several drugs in early development have great potential.
...

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In this relatively brief study, the apparently increased comparative risk of agranulocytosis requires that the use of clozapine be limited to selected treatment-resistant patients.

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It is suggested that clozapine's beneficial effects in schizophrenia may be achieved, in part, through D4-mediated GABA modulation, possibly implicating disinhibition of excitatory transmission in intrinsic cortical, thalamocortical and extrapyramidal pathways.

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TLDR
These findings suggest that the putative D4 receptors are not synthesized in this region, but are presynaptically localized on striatal afferent terminals, which is inconsistent with mRNA studies that have shown negligible amounts in striatum and accumbens.

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It is concluded that the combined density of D2 and D3 receptors (labelled by [3H]raclopride) is increased by only 10% in schizophrenia brain, as found by Farde et al.15, but that it is the density of dopamine D4 receptors which is sixfold elevated in schizophrenia.

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