D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs

@article{Roth2006D4DR,
  title={D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs},
  author={Bobbie Lee Roth and Sweta Tandra and Loyd H. Burgess and David R. Sibley and Herbert Y. Meltzer},
  journal={Psychopharmacology},
  year={2006},
  volume={120},
  pages={365-368}
}
The affinities of 13 atypical and 12 typical antipsychotic drugs for the cloned rat D4 dopamine receptor and the D4/D2 ratios were examined. Of the atypical antipsychotic drugs tested, only clozapine, risperidone, olanzapine, zotepine and tiospirone had affinities less than 20 nM. In fact, many atypical antipsychotic drugs had relatively low affinities for the cloned rat D4 receptor, with Ki values greater than 100 nM (Seroquel, fluperlapine, tenilapine, FG5803 and melperone). Additionally… Expand
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References

SHOWING 1-10 OF 25 REFERENCES
Dopamine D4 versus D2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications.
TLDR
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
Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine
TLDR
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. Expand
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.
TLDR
The authors examined the affinities of 36 typical and atypical antipsychotic agents for the cloned rat 5-hydroxytryptamine-6 and rat5-HT7 receptors in transiently expressed COS-7 cells or stably transfected HEK-293 cells to identify those with high affinity for the newly discovered 5-HT6 receptor. Expand
Dopamine neurochemical profile of atypical antipsychotics resembles that of D-1 antagonists
TLDR
Dopamine release and metabolism were determined after the oral administration of antipsychotic drugs at doses equal to or sixfold greater than the ED50 dose for their inhibition of apomorphine-induced climbing, suggesting that a mechanism related to D-1 receptor antagonism may contribute to the action of atypical antipsychotics. Expand
Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values.
The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor bindingExpand
Binding of typical and atypical antipsychotic agents to transiently expressed 5-HT1C receptors.
TLDR
The results indicate that although several putative atypical antipsychotic agents have high affinities for the cloned rat 5-HT1C receptor, the spectrum of drug binding does not correlate with the atypicals nature of these compounds. Expand
In vivo potencies of antipsychotic drugs in blocking alpha 1 noradrenergic and dopamine D2 receptors: implications for drug mechanisms of action.
TLDR
Preliminary experiments with this in vivo model suggest that all antipsychotic drugs are effective antagonists at alpha 1 noradrenergic receptors, while not all areeffective antagonists at dopamine D2 receptors. Expand
Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells.
TLDR
Clozapine's unusual efficacy in refractory schizophrenic patients and its low incidence of extrapyramidal side effects may be explained, but because most other atypical neuroleptics studied lacked high affinity and selectivity at muscarinic receptor subtypes, it is likely that other mechanisms are involved as well. Expand
5-HT2 receptor blockade by ICI 169,369 and other 5-HT2 antagonists modulates the effects of D-2 dopamine receptor blockade.
TLDR
The blockade of D-2 receptors by haloperidol results in a compensatory increase in rat striatal DA metabolism, which is enhanced by ICI 169,369, and data suggest that the 5-HT2 component of these compounds, by enhancingDA metabolism, may act to attenuate the blockade of striatal D- 2 receptors by these compounds. Expand
Pharmacological and functional characterization of D2, D3 and D4 dopamine receptors in fibroblast and dopaminergic cell lines.
In order to study the properties of the D2-like dopamine receptors, D2, D3 and D4 clones were transfected into mouse Ltk- fibroblasts, CCL1.3, and a neuronal mesencephalic cell line, MN9D. Most ofExpand
...
1
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