Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia.
BACKGROUND
Both traditional and atypical antipsychotics have been hypothesised to be effective in schizophrenia through limbic and cortical D(2) dopamine receptor blockade.


OBJECTIVE
To investigate this hypothesis with the D(2)/D(3)-selective positron emission tomography (PET) probe [(76)Br]-FLB457.


METHODS
PET scans were performed on 6 controls and 18 patients with schizophrenia treated with haloperidol or with risperidone, clozapine, amisulpride or olanzapine.


RESULTS
The D(2) dopamine receptor blockade was high in the temporal cortex with both haloperidol and atypical antipsychotics. The atypicals, however, induced a significantly lower D(2) binding index than haloperidol in the thalamus and in the striatum.


CONCLUSIONS
Results suggest that cortical D(2) dopamine receptors are a common target of traditional and atypical antipsychotics for therapeutic action. Higher in vivo binding to the D(2) receptors in the cortex than in the basal ganglia is suggested as an indicator of favourable profile for a putative antipsychotic compound.
Xiberas
X
X
INSERM U 334, Service Hospitalier Frédéric Joliot. A. Chenevier Hôpital, Créteil, France.
Martinot
J L
JL
Mallet
L
L
Artiges
E
E
Loc'H
C
C
Mazière
B
B
Paillère-Martinot
M L
ML
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006220:Haloperidol / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D006220:Haloperidol