D(2) and 5HT(2A) receptor occupancy of different doses of quetiapine in schizophrenia: a PET study.
OBJECTIVE
Quetiapine is a novel antipsychotic agent with many atypical features, including low D(2) and higher 5HT(2A) affinity in vitro, low propensity to induce extra-pyramidal side effects and minimal effects on prolactin levels. The purpose of this study was to investigate, using positron emission tomography (PET), the relationship between plasma concentrations of different doses of quetiapine and occupancy of D(2) and 5HT(2A) receptors in schizophrenic patients.


METHODS
Five patients were treated with quetiapine (titrated to 750 or 450 mg/day) for 28 days, subsequently reduced weekly in a descending-dose schedule. Dopamine D(2) and 5HT(2A) occupancies were determined using [(11)C] raclopride and [(11)C] N-methylspiperone as ligands, respectively, and PET imaging.


RESULTS
Mean D(2) receptor occupancies of 41 and 30% were observed at quetiapine doses of 750 and 450 mg/day. At lower dose levels no occupancy could be determined. Quetiapine induced a consistently higher degree of 5HT(2A) receptor occupancy, with mean occupancies of 74 and 57% at doses of 750 and 450 mg/day, respectively. No EPS emerged during the trial and most of the pre-trial EPS resolved during the study.


CONCLUSIONS
In clinically effective doses, quetiapine induced low occupancy at D(2) receptors, which is consistent with atypical antipsychotics such as clozapine, and probably explains the lack of EPS observed in this trial. Correlations between receptor occupancy and plasma concentrations of quetiapine could not be calculated, although receptor occupancy increased with higher plasma concentrations for the 450 and 750 mg doses.
Gefvert
O
O
Department of Psychiatric Research, Central Hospital, S-721 89, Västerås, Sweden. ola.gefvert@ltvastmanland.se
Lundberg
T
T
Wieselgren
I M
IM
Bergström
M
M
Långström
B
B
Wiesel
F
F
Lindström
L
L
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D000069348:Quetiapine Fumarate; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D000069348:Quetiapine Fumarate