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

  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},

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

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

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

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

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

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
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.



The effects of a selective D4 dopamine receptor antagonist (L-745,870) in acutely psychotic inpatients with schizophrenia. D4 Dopamine Antagonist Group.

The selective D4 dopamine receptor antagonist L-745,870 was ineffective as an antipsychotic for the treatment of neuroleptic responsive inpatients with acute schizophrenia.

Pharmacological characterization of U-101387, a dopamine D4 receptor selective antagonist.

The results demonstrate that the D4-selective antagonist, U-101387, produces effects that are distinct from those of the nonselective D2 antagonists as well as D3-preferring agents.

Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine.

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.

Localization of dopamine D4 receptors in GABAergic neurons of the primate brain

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.

Distribution of putative D4 dopamine receptors in postmortem striatum from patients with schizophrenia

  • A. MurrayT. Hyde J. Kleinman
  • Biology, Psychology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1995
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.

Dopamine D4 receptors elevated in schizophrenia

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.

The role of dopamine D4 receptor in the induction of behavioral sensitization to amphetamine and accompanying biochemical and molecular adaptations.

D dopamine D4 receptors play an important role in the induction of behavioral sensitization to Amp and accompanying adaptations in pre- and postsynaptic neural systems associated with the mesolimbocortical dopamine projections, and concurrent administration of PNU-101387G with Amp during pretreatment blocked the augmentation in Amp-induced dopamine release.