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

@article{Tol1991CloningOT,
  title={Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine},
  author={Hubert H.M. Van Tol and James R. Bunzow and H C Guan and Roger K. Sunahara and Philip Seeman and Hyman B. Niznik and Olivier Civelli},
  journal={Nature},
  year={1991},
  volume={350},
  pages={610-614}
}
DOPAMINE receptors belong to the family of G protein-coupled receptors. On the basis of the homology between these receptors, three different dopamine receptors (D1,D2,D3) have been cloned1–7. Dopamine receptors are primary targets for drugs used in the treatment of psychomotor disorders such as Parkinson's disease and schizophrenia8,9. In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine10 is one of the most favoured antipsychotics because it does not cause… Expand
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The overall D2 characteristics, plus the anomalous divergence from these characteristics, make the D4 receptor a highly attractive candidate for the dopamine receptor abnormality of schizophrenia. Expand
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The therapeutic potential of D4 receptors as a target for developing antipsychotics will be known only when selective D4 receptor antagonists with varying D2/D4 and D4/5‐HT2A ratios are developed and tested in psychiatric patients. Expand
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The results of this study suggest that inherited variants of D4 may explain some of the interindividual variation seen in patient response to different classes of antipsychotic medication. Expand
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  • Medicine
  • Pharmacology & therapeutics
  • 2001
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Because of distinct aspects of regulation of the D3 receptor, it represents a unique target for therapeutic intervention in schizophrenia without high potential for unintended side effects such as tardive dyskinesia. Expand
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The results suggest the D3 receptor as an important target for antipsychotic drug action, and D2/D3 receptor selective antagonists as promising therapeutic agents. Expand
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TLDR
It is demonstrated that pipamperone, an antipsychotic, acts as a pharmacological chaperone and by doing so, increases the expression level of the dopamine D4 receptor. Expand
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The genetic linkage study in a large Italian kindred segregating schizophrenia showed significant evidence for exclusion for linkage between schizophrenia and the dopamine D4 receptor gene and the TH gene under the models specified. Expand
Dopamine D4 versus D2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications.
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The results with the antipsychotic agents tested, support the concept that dopamine D4 receptor selectivity may confer clozapine-like antipsychotics efficacy and furthermore that dopamineD2 receptor selectiveness may confer side effect liability (extrapyramidal side effects and tardive dyskinesia). Expand
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