In vivo determination of striatal dopamine D2 receptor occupancy in patients treated with olanzapine.
In vivo studies of dopamine D2 receptor occupancy with atypical antipsychotics have suggested good clinical efficacy at occupancy rates less than those observed with typical neuroleptics, and few extrapyramidal side effects (EPS), possibly even at high levels of D2 occupancy. We used [123I]IBZM-SPECT to investigate striatal D2 receptor occupancy in 10 schizophrenic patients who were treated with both a low (5 mg) and a high dose (20 mg) of the novel antipsychotic olanzapine without concomitant medications. The mean D2 occupancy at 5 mg was 59.8% (range 33-81%); the mean D2 occupancy at 20 mg was 82.8% (range 56-97%). Although the D2 occupancy rates on 5 and 20 mg olanzapine were significantly different (P < 0.001), there were no significant differences in clinical ratings for psychiatric symptoms or extrapyramidal side effects between the two doses of olanzapine. These data suggest that: (1) olanzapine doses below those used routinely occupy D2 receptors at levels approaching those associated with therapeutic response; (2) higher doses produce relatively high levels of D2 occupancy rates; and (3) EPS are mild even at relatively high levels of D2 occupancy.
Raedler
T J
TJ
Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
Knable
M B
MB
Lafargue
T
T
Urbina
R A
RA
Egan
M F
MF
Pickar
D
D
Weinberger
D R
DR
D000328:Adult; D001549:Benzamides; D001569:Benzodiazepines; D016022:Case-Control Studies; D003287:Contrast Media; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D001569:Benzodiazepines; D003287:Contrast Media; D000077152:Olanzapine; D010890:Pirenzepine; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D017367:Selective Serotonin Reuptake Inhibitors; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide