No support for regional selectivity in clozapine-treated patients: a PET study with [(11)C]raclopride and [(11)C]FLB 457.
OBJECTIVE
The authors' goal was to test the hypothesis of extrastriatal D(2) receptor selectivity as the mechanism of action of clozapine.


METHODS
Positron emission tomography (PET) was used to examine extrastriatal as well as striatal dopamine D(2) receptor occupancy in four patients treated with clozapine and three patients treated with haloperidol. The reference radioligand [(11)C]raclopride was used for determination of D(2) receptor occupancy in the striatum. The radioligand [(11)C]FLB 457 was chosen for determination of D(2) receptor occupancy in the thalamus, the temporal cortex, and the frontal cortex.


RESULTS
In patients treated with haloperidol the D(2) receptor occupancy was high in all examined brain regions. In clozapine-treated patients the D(2) receptor occupancy was relatively low in both the striatum and the extrastriatal regions.


CONCLUSIONS
The results from the present study give no support for the hypothesis of regional selectivity as the mechanism of action for clozapine.
Talvik
M
M
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-171 76 Stockholm, Sweden. mirjam.talvik@nvso.sll.se
Nordström
A L
AL
Nyberg
S
S
Olsson
H
H
Halldin
C
C
Farde
L
L
D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism*; D012457:Salicylamides; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D012563:Schizophrenia, Paranoid / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000706:statistics & numerical data*
D014150:Antipsychotic Agents; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457; D020891:Raclopride; D003024:Clozapine; D006220:Haloperidol