Extrastriatal dopamine D(2) receptor occupancy in olanzapine-treated patients with schizophrenia.
Olanzapine is described as a multi-acting receptor-targeted antipsychotic agent. Although regional differences of dopamine D(2) receptor occupancy, i.e., limbic selectivity, were reported for olanzapine, contradictory results were also reported. We measured dopamine D(2) receptor occupancy of olanzapine in extrastriatal regions in patients with schizophrenia using positron-emission tomography with [(11)C]FLB457 and the plasma concentrations of olanzapine. Ten patients with schizophrenia taking 5-20 mg/day of olanzapine participated. Dopamine D(2) receptor occupancy in the temporal cortex ranged from 61.1 to 85.8%, and plasma concentration was from 12.7 to 115.4 ng/ml. The ED(50) value was 3.4 mg/day for dose and 10.5 ng/ml for plasma concentration. The ED(50) values obtained in this study were quite similar to those previously reported in the striatum. In conclusion, although the subjects and methods were different from previous striatal occupancy studies, these results suggest that limbic occupancy by olanzapine may not be so different from that in the striatum.
Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, 263-8555, Japan.
Ryosuke
R
Arakawa
Hiroshi
H
Ito
Masaki
M
Okumura
Akihiro
A
Takano
Hidehiko
H
Takahashi
Harumasa
H
Takano
Yoshiro
Y
Okubo
Tetsuya
T
Suhara
D000328:Adult; D001569:Benzodiazepines / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008875:Middle Aged; D000077152:Olanzapine; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000493:pharmacokinetics; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
D001569:Benzodiazepines; D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D000077152:Olanzapine; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D017367:Selective Serotonin Reuptake Inhibitors; C065065:FLB 457