title: Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol.
abstract: There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D(2)/D(3) receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors. We performed [(18)F] fallypride PET studies in six schizophrenic subjects treated with olanzapine and six schizophrenic subjects treated with haloperidol to examine the occupancy of striatal and extrastriatal dopamine receptors by these antipsychotic drugs. [(18)F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT(2A) receptor occupancy. Occupancy of dopamine D(2)/D(3) receptors by olanzapine was not significantly different from that seen with haloperidol in the putamen, ventral striatum, medial thalamus, amygdala, or temporal cortex, that is, 67.5-78.2% occupancy; olanzapine produced no preferential occupancy of dopamine D(2)/D(3) receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D(2)/D(3) receptors in olanzapine-treated compared to haloperidol-treated subjects, that is, 40.2 vs 59.3% (p=0.0014, corrected for multiple comparisons); in olanzapine-treated subjects, the substantia nigra/VTA was the only region with significantly lower dopamine D(2)/D(3) receptor occupancy than the putamen, that is, 40.2 vs 69.2% (p<0.001, corrected for multiple comparison). Occupancy of 5-HT(2A) receptors was 85-93% in the olanzapine- treated subjects. The results of this study demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D(2)/D(3) receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.
authors.affiliation: Department of Radiology, Vanderbilt University School of Medicine, University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA. robert.kessler@vanderbilt.edu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kessler
authors.forename: Mohammad Sib
authors.initials: MS
authors.lastname: Ansari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Riccardi
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Karuna
authors.initials: K
authors.lastname: Jayathilake
authors.forename: Benoit
authors.initials: B
authors.lastname: Dawant
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001549:Benzamides; D001569:Benzodiazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D049268:Positron-Emission Tomography; D011744:Pyrimidinones; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000187:drug effects*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism; D012702:Serotonin Antagonists
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D018492:Dopamine Antagonists; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011744:Pyrimidinones; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D050637:Receptors, Dopamine D3; D012702:Serotonin Antagonists; D001569:Benzodiazepines; C045359:setoperone; D006220:Haloperidol; D000077152:Olanzapine