Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine.
OBJECTIVE
Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second-generation antipsychotics in dopamine D(2) receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D(2/3) receptor apparent binding potential (BP(app)) and occupancy in midbrain and temporal cortex among clozapine-, olanzapine- and haloperidol-treated schizophrenia patients.


METHODS
Dopamine D(2/3) binding was studied on single-photon emission computed tomography ligand [(123)I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug-naïve patients and seven healthy controls.


RESULTS
Statistically significant differences in midbrain dopamine D(2/3) receptor BP(app) (P = 0.015) and occupancy (P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine-treated patients (5%), followed by olanzapine-treated patients (28%), compared to haloperidol-treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug-naïve vs healthy controls) in the examined brain areas (P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used.


CONCLUSIONS
Both typical and second-generation antipsychotics occupy cortical dopamine D(2/3) receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D(2/3) occupancy between classical antipsychotics and second-generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.
Tuppurainen
Heli
H
Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland. heli.tuppurainen@niuva.fi
Kuikka
Jyrki T
JT
Viinamäki
Heimo
H
Husso
Minna
M
Tiihonen
Jari
J
D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001549:Benzamides; D001569:Benzodiazepines / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D003024:Clozapine / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006220:Haloperidol / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D000077152:Olanzapine; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C063525:epidepride; D001569:Benzodiazepines; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine