Striatal and extra-striatal D(2)/D(3) dopamine receptor occupancy by quetiapine in vivo. [(123)I]-epidepride single photon emission tomography(SPET) study.
BACKGROUND
Selective action at limbic cortical dopamine D(2)-like receptors could mediate atypical antipsychotic efficacy with few extrapyramidal side-effects.


OBJECTIVE
To test the hypothesis that quetiapine has 'limbic selective' D(2)/D(3) receptor occupancy in vivo.


METHODS
The high-affinity D(2)/D(3) ligand [(123)I]-epidepride and single photon emission tomography were used to estimate D(2)/D(3) specific binding and an index of relative percentage D(2)/D(3) occupancy in striatal and temporal cortical regions for quetiapine-treated patients (n=6). Quetiapine-, and previously studied typical-antipsychotic- and clozapine-treated patients were compared.


RESULTS
Mean (s.d.) relative percentage D(2)/D(3) receptor occupancy by quetiapine was 32.0% (14.6) in striatum and 60.1% (17.2) in temporal cortex (mean daily dose 450 mg: range 300-700 mg/day). Quetiapine treatment resulted in limbic selective D(2)/D(3) blockade similar to clozapine and significantly higher than typical antipsychotics.


CONCLUSIONS
Preliminary data suggest that limbic selective D(2)/D(3) receptor blockade is important for atypical drug action.
Stephenson
C M
CM
Institute of Psychiatry, London.
Bigliani
V
V
Jones
H M
HM
Mulligan
R S
RS
Acton
P D
PD
Visvikis
D
D
Ell
P J
PJ
Kerwin
R W
RW
Pilowsky
L S
LS
D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism*; D001549:Benzamides; D003024:Clozapine / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D003987:Dibenzothiazepines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D000069348:Quetiapine Fumarate; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D001549:Benzamides; C493593:DRD3 protein, human; D003987:Dibenzothiazepines; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C063525:epidepride; D000069348:Quetiapine Fumarate; D003024:Clozapine