Occupancy of dopamine D2 receptors by the atypical antipsychotic drugs risperidone and olanzapine: theoretical implications.
BACKGROUND
To examine the D2 occupancy of two commonly used antipsychotic medications and relate this to the D2 occupancy by endogenous dopamine in schizophrenia.


OBJECTIVE
The aim of this study is to compare the occupancy of striatal D2 receptors by the atypical antipsychotic medications risperidone and olanzapine at fixed dosages and to estimate the effect on D2 occupancy by dopamine as a result of these treatments.


METHODS
Seven patients with schizophrenia taking risperidone 6 mg/day and nine patients with schizophrenia taking olanzapine 10 mg/day underwent an [123I]IBZM SPECT scan after 3 weeks of treatment. The specific to non-specific equilibrium partition coefficient (V3") after bolus plus constant infusion of the tracer was calculated as [(striatal activity)/(cerebellar activity)]-1. D2 receptor occupancy was calculated by comparing V3" measured in treated patients to an age-corrected V3" value derived from a group of untreated patients with schizophrenia, previously published, according to the following formula: OCC=1-(V3" treated/V3" drug free).


RESULTS
V3" was significantly lower in risperidone treated patients compared with olanzapine treated patients (0.23+/-0.06 versus 0.34+/-0.08, P=-0.01), which translated to a significantly larger occupancy in schizophrenic patients treated with risperidone compared to olanzapine (69+/-8% versus 55 +/-11%, P=0.01). Data from our previous study were used to calculate the occupancy of striatal D2 receptors by antipsychotic medications required to reduce the occupancy of these receptors by endogenous dopamine to control values. In medication-free patients with schizophrenia, the occupancy of striatal D2 receptors by endogenous dopamine is estimated at 15.8%. In healthy controls, the occupancy of striatal D2 receptors by dopamine is estimated at 8.8%. In order to reduce the dopamine occupancy of striatal D2 receptors in patients with schizophrenia to control values, 48% receptor occupancy by antipsychotic medications is required.


CONCLUSIONS
These data indicate that the dosage of these medications, found to be effective in the treatment of schizophrenia, reduces DA stimulation of D2 receptors to levels slightly lower than those found in unmedicated healthy subjects.
Frankle
W G
WG
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA. wf2004@columbia.edu
Gil
R
R
Hackett
E
E
Mawlawi
O
O
Zea-Ponce
Y
Y
Zhu
Z
Z
Kochan
L D
LD
Cangiano
C
C
Slifstein
M
M
Gorman
J M
JM
Laruelle
M
M
Abi-Dargham
A
A
D000328:Adult; D000465:Algorithms; D014150:Antipsychotic Agents / Q000378:metabolism*; D001549:Benzamides; D001569:Benzodiazepines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018967:Risperidone / Q000494:pharmacology*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D001549:Benzamides; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D018967:Risperidone; D000077152:Olanzapine; D004298:Dopamine