Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition

  title={Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition},
  author={Robert S. Mansbach and Elizabeth W. Brooks and Mark A. Sanner and Stevin H. Zorn},
Abstract Recent evidence suggests that the dopamine D4 receptor may play a role in schizophrenia, and that the atypical properties of the antipsychotic clozapine may be attributable in part to its antagonistic actions at this receptor. In the present study, clozapine and three other compounds having D4 dopamine receptor antagonist properties were examined for their effectiveness in reducing losses in prepulse inhibition (PPI) induced in rats by the dopamine receptor agonist apomorphine… 

Actions of Novel Antipsychotic Agents on Apomorphine-Induced PPI Disruption: Influence of Combined Serotonin 5-HT1A Receptor Activation and Dopamine D2 Receptor Blockade

Antipsychotics possessing agonist efficacy at 5-HT1A receptors exhibit diverse profiles against apomorphine-induced PPI deficits, depending on the balance between D2 and 5- HT1A activities, suggesting that they may display distinct activity on some aspects of gating deficits in schizophrenic patients.

FAUC 213, a highly selective dopamine D4 receptor full antagonist, exhibits atypical antipsychotic properties in behavioural and neurochemical models of schizophrenia

Evidence is gathered that FAUC 213 exhibits atypical antipsychotic characteristics and is not believed to mediate the above-mentioned effects via D2 receptor antagonism, but a partial involvement of 5-HT2- and α1-receptors cannot be ruled out at present.

Buspirone Counteracts MK-801-Induced Schizophrenia-Like Phenotypes through Dopamine D3 Receptor Blockade

Results indicate, for the first time, that buspirone, through its D3R antagonist activity, may be a useful tool for improving the treatment of cognitive deficits in schizophrenia.

Selective dopamine D4 receptor antagonists

Recent findings with new biological models and D4 selective agonists may help clarify the role of the D4 receptor in the aetiology of schizophrenia.

Disruption of prepulse inhibition of the startle reflex by the preferential D3 agonist ropinirole in healthy males

Results suggest a role for the dopamine D3 receptor in the mediation of human PPI, although a contribution from ropinirole’s agonistic activity at the D2 receptor cannot be entirely excluded.

Dopamine D4 receptor stimulation contributes to novel object recognition: Relevance to cognitive impairment in schizophrenia

D4 receptor agonism has a beneficial effect on novel object recognition in sub-chronic PCP-treated rats and augments the cognitive enhancing efficacy of an atypical antipsychotic drug that lacks affinity for the D4 receptor, lurasidone.



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 and haloperidol in an animal model of sensorimotor gating deficits in schizophrenia

Multiple serotonin receptor subtypes modulate prepulse inhibition of the startle response in rats

Effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine inhibition of sensorimotor gating of the startle response in the rat.

The present findings suggest that the activation of D2 dopamine receptors is responsible for the loss of PPI in rats, and overactivity of D 2 dopamine receptors might also be a substrate for PPI deficits in schizophrenia.

Dopamine receptor pharmacology.

Dopamine receptors are the primary targets in the treatment of schizophrenia, Parkinson's disease, and Huntington's chorea, and are discussed in this review by Philip Seeman and Hubert Van Tol.

Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine

The cloning of a gene that encodes a dopamine receptor gene that has high homology to the human dopamine D2 and D3 receptor genes is reported, which suggests the existence of other types of dopamine receptors which are more sensitive to clozapine.

Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4.

  • P. Seeman
  • Psychology, Medicine
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1992
An analysis of the literature indicates that therapeutic concentrations of antipsychotic drugs act primarily at D2 receptors, with the exception of clozapine, which acts at D4 receptors.