Dopamine D-2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas

作者：Vernaleken Ingo^*; Janouschek Hildegard; Raptis Mardjan; Hellmann Sandra; Veselinovic Tanja; Broecheler Anno; Boy Christian; Cumming Paul; Hiemke Christoph; Roesch Frank; Schaefer Wolfgang M; Gruender Gerhard

来源：International Journal of Neuropsychopharmacology, 2010, 13(7): 951-960.

DOI：10.1017/S1461145710000374

• Antipsychotics
• D-2/3 receptor occupancy
• positron emission tomography
• preferential extrastriatal binding
• quetiapine
• schizophrenia

Quetiapine is next to clozapine an antipsychotic agent that exerts hardly any extrapyramidal side-effects at clinical efficacious doses. Some previous receptor occupancy studies reported preferential extrastriatal D-2/3 receptor (D2/3R)-binding properties of second-generation antipsychotics and suggested this as possible reason for improved tolerability. This positron emission tomography (PET) investigation was designed to compare the occupancy of dopamine D(2/3)Rs by quetiapine in striatal and extrastriatal brain regions. Therefore, a cohort of 16 quetiapine-treated psychotic patients underwent an [F-18]fallypride (FP) PET scan. Due to the high affinity of FP and its comparatively long half-life, striatal and extrastriatal binding potentials could be determined in one single scan. Receptor occupancy was calculated as percent reduction in binding potential relative to age-matched medication-free patients suffering from schizophrenia. Quetiapine occupied 44 +/- 18% in the temporal cortex and 26 +/- 17% in the putamen, a difference significant at the level of p = 0.005 (Student's t test). Quetiapirte showed a mean occupancy of 36 +/- 16% and in the thalamus. In the caudate nucleus there was an occupancy of 29 +/- 16% (p =0.0072). Individual occupancy levels did not exceed 59% in any of the striatal volumes of interest. The time-interval between scan and last drug ingestion did not influence the relationship between plasma concentration and central D2/3R occupancy. Taken together, quetiapine shows preferential extrastriatal binding at D(2/3)Rs; the extent of this difference is comparable to that previously described for clozapine. Both antipsychotics show very low affinity for D(2/3)Rs.

• 出版日期2010-8