In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs. [123I]epidepride single photon emission tomography (SPET) study.
BACKGROUND
The dopamine hypothesis proposes that antipsychotic drugs act primarily through limbic cortical D2/D2-like dopamine receptor blockade.


OBJECTIVE
To evaluate this hypothesis with the D2/D3-selective SPET probe [123I]-epidepride.


METHODS
[123I]-epidepride SPET scans were performed on 12 patients with schizophrenia treated with antipsychotics and II age-matched healthy controls. [123I]-epidepride 'specific binding' to D2/D3 dopamine receptors was estimated, and relative percentage D2/D3 receptor occupancy by typical antipsychotic drugs determined.


RESULTS
Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equivalents. Mean percentage D2/D3 receptor occupancy was 81.6 (8.1) and 73.2 (13.9) in the temporal cortex and striatum respectively.


CONCLUSIONS
Typical antipsychotic drug treatment is associated with substantial temporal cortical D2/D3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia.
Bigliani
V
V
Institute of Psychiatry, London.
Mulligan
R S
RS
Acton
P D
PD
Visvikis
D
D
Ell
P J
PJ
Stephenson
C
C
Kerwin
R W
RW
Pilowsky
L S
LS
D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001549:Benzamides; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods
D014150:Antipsychotic Agents; D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C063525:epidepride