title: Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine.
abstract: 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.
authors.affiliation: Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland. heli.tuppurainen@niuva.fi
authors.forename: Heli
authors.initials: H
authors.lastname: Tuppurainen
authors.forename: Jyrki T
authors.initials: JT
authors.lastname: Kuikka
authors.forename: Heimo
authors.initials: H
authors.lastname: Viinamäki
authors.forename: Minna
authors.initials: M
authors.lastname: Husso
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
mesh_terms: 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
chemical_list: 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