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

  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},
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 In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine10 is one of the most favoured antipsychotics because it does not cause… 
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1
The cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned Dt receptor is reported here the existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.
Multiple dopamine D4 receptor variants in the human population
This is the first report of a receptor in the catecholamine receptor family that displays polymorphic variation in the human population and such variation among humans may underlie individual differences in susceptibility to neuropsychiatric disease and in responsiveness to 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.
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.


Molecular cloning and expression of the gene for a human D1 dopamine receptor
Transient or stable expression of the cloned gene in host cells established specific ligand binding and functional activity characteristic of a D1 dopamine receptor coupled to stimulation of adenylyl cyclase.
Human dopamine D1 receptor encoded by an intronless gene on chromosome 5
The cloning of the D1 receptor gene is reported, which resides on an intronless region on the long arm of chromosome 5, near two other members of the G-linked receptor family, and binds drugs with affinities identical to the native human D1 receptors.
Cloning and expression of human and rat Dt dopamine receptors
The cloning of human and rat D1 dopamine receptors by applying an approach based on the polymerase chain reaction is reported, which reveals that it is a G protein-coupled receptor.
Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics
The D3 receptor is localized to limbic areas of the brain, which are associated with cognitive, emotional and endocrine functions, and seems to mediate some of the effects of antipsychotic drugs and drugs used against Parkinson's disease.
The dopamine D2 receptor: two molecular forms generated by alternative splicing.
Results from polymerase chain reactions as well as in situ hybridization revealed that mRNA encoding both receptor forms is present in pituitary and brain of both rat and man, and the two receptor forms are generated by differential splicing possibly to permit coupling to different G proteins.
Atypical neuroleptics: role of multiple receptors, endogenous dopamine, and receptor linkage
  • P. Seeman
  • Psychology
    Acta psychiatrica Scandinavica. Supplementum
  • 1990
The atypical nature of the benzamides may be based on their sensitivity to the level of endogenous dopamine released in the different regions of the brain, which may possibly stem from direct linkage between different receptors coupled through components of the G protein system.
Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases.
  • P. Seeman, N. Bzowej, W. Tourtellotte
  • Psychology, Medicine
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1987
Cloning of the cDNA and gene for a human D2 dopamine receptor.
A clone encoding a human D2 dopamine receptor was isolated from a pituitary cDNA library and sequenced, and it was shown that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitsary receptor are encoded by a single exon of 87 base pairs.
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.