Multiple dopamine D4 receptor variants in the human population

@article{Tol1992MultipleDD,
  title={Multiple dopamine D4 receptor variants in the human population},
  author={Hubert H.M. Van Tol and Caren M. Wu and H C Guan and Koichi Ohara and James R. Bunzow and Olivier Civelli and James L. Kennedy and Philip Seeman and Hyman B. Niznik and Vera Jovanovic},
  journal={Nature},
  year={1992},
  volume={358},
  pages={149-152}
}
THE dopamine D4 receptor structurally and pharmacologically resembles the dopamine D2 and D3 receptors1–5. Clozapine, an atypical antipsychotic that is relatively free of the adverse effects of drug-induced parkinsonism and tardive dyskinesia6,7, binds to the D4 receptor with an affinity 10 times higher than to the D2 and D3 receptors1. This may explain clozapine's atypical properties. Here we report the existence of at least three polymorphic variations in the coding sequence of the human D4… 

Polymorphisms of the dopamine D4 receptor and response to antipsychotic drugs

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.

The dopamine D4 receptor in schizophrenia: an update

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.

Dopamine D4 receptors and development of newer antipsychotic drugs

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.

Dopamine D4 Receptors

As novel serotonin-dopamine receptor antagonists with defined pharmacological profiles become available, the careful analysis of the relationship between receptor binding profiles and efficacy will determine the most important receptor targets for improved antipsychotic action without the generation of EPS.

Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia.

None of the 147 Caucasians (113 controls; 34 schizophrenics) revealed this variant, termed D4GLYCINE194, which occurs one amino acid away from a serine amino acid which is critical for the attachment of dopamine.

Dopamine D4 receptor variant in Africans, D4valine194glycine, is insensitive to dopamine and clozapine: report of a homozygous individual.

It was found that the D4Valine194Glycine receptor was two orders of magnitude less sensitive to dopamine, clozapine and olanzapine, and the variant receptor was insensitive to guanine nucleotide, indicating the absence of a high-affinity state or functional state.

Analysis of the D4 dopamine receptor gene variant in an Italian schizophrenia kindred.

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.
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