Dose–Occupancy Study of Striatal and Extrastriatal Dopamine D2 Receptors by Aripiprazole in Schizophrenia with PET and [18F]Fallypride

@article{Kegeles2008DoseOccupancySO,
  title={Dose–Occupancy Study of Striatal and Extrastriatal Dopamine D2 Receptors by Aripiprazole in Schizophrenia with PET and [18F]Fallypride},
  author={Lawrence S. Kegeles and Mark Slifstein and W. Gordon Frankle and Xiaoyan Xu and Elizabeth Hackett and Sung-A. Bae and Robyn Gonzales and Jong‐Hoon Kim and Beatriz Alvarez and Roberto Gil and Marc Laruelle and Anissa Abi-Dargham},
  journal={Neuropsychopharmacology},
  year={2008},
  volume={33},
  pages={3111-3125}
}
Positron emission tomography (PET) and the high affinity D2/3 radiotracer [18F]fallypride allow the assessment of D2/3 receptor occupancy of antipsychotic drugs in striatal and extrastriatal brain regions. We measured regional occupancy attained across a range of clinical dosing by the partial D2 agonist aripiprazole using these methods. Twenty-eight PET scans were acquired on the ECAT EXACT HR+ camera in 19 patients with schizophrenia or schizoaffective disorder. Daily aripiprazole doses… 

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...

References

SHOWING 1-10 OF 56 REFERENCES

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

TLDR
The occupancy of D2/D3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozAPine binds preferentially to extrastriatal dopamine receptors.

Striatal Vs Extrastriatal Dopamine D2 Receptors in Antipsychotic Response—A Double-Blind PET Study in Schizophrenia

TLDR
D dopamine D2 blockade within specific regions of the striatum may be most critical for ameliorating psychosis in schizophrenia, when combined with the preclinical data implicating the mesolimbic striatum in antipsychotic response.

A PET-study of [11C]FLB 457 binding to extrastriatal D2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients

TLDR
The study shows that [11C]FLB 457 has potential for quantitative PET-examination of D2-dopamine receptors in man and to determine extrastriatal D 2-receptor occupancy in antipsychotic drug-treated patients.

Occupancy of Striatal and Extrastriatal Dopamine D2/D3 Receptors by Olanzapine and Haloperidol

TLDR
It is demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D2/D3 receptors but does spare substantia nigra/VTA receptors, which may contribute to the low incidence of extrapyramidal side effects in olanZapine-treated patients.

Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia.

TLDR
Clozapine, at doses known to be effective in routine clinical settings, showed a D 2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antippsychotics.

Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects.

TLDR
This finding indicates that neuroleptic-induced extrapyramidal syndromes are related to the degree of central D2 occupancy induced in the basal ganglia of drug-treated schizophrenic patients and demonstrates that clozapine is also "atypical" with respect to the central D1 occupancy in patients.

Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia.

TLDR
The study confirms that D(2) occupancy is an important mediator of response and side effects in antipsychotic treatment, and is consistent with a "target and trigger" hypothesis of antipsychotics action.

In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs

TLDR
Typical antipsychotic drug treatment is associated with substantial temporal cortical D2/D3 receptor occupancy and the relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia.

In Vivo Extrastriatal and Striatal D2 Dopamine Receptor Blockade by Amisulpride in Schizophrenia

TLDR
Dose-dependent differential binding profiles of amisulpride to D2 receptors in extrastriatal and striatal regions were demonstrated, and two therapeutic ranges of plasma concentrations for negative and positive schizophrenic symptoms, respectively, are suggested.
...