Optimizing Limbic Selective D2/D3 Receptor Occupancy by Risperidone: A [123I]-Epidepride SPET Study
作者:
Rodrigo Bressan,
Kjell Erlandsson,
Hugh Jones,
Rachel Mulligan,
Peter Ell,
Lyn Pilowsky,
期刊:
Journal of Clinical Psychopharmacology
(OVID Available online 2003)
卷期:
Volume 23,
issue 1
页码: 5-14
ISSN:0271-0749
年代: 2003
出版商: OVID
数据来源: OVID
摘要:
Selective action at limbic cortical dopamine D2-like receptors is a putative mechanism of atypical antipsychotic efficacy with few extrapyramidal side effects. Although risperidone is an atypical antipsychotic with high affinity for D2receptors, low-dose risperidone treatment is effective without inducing extrapyramidal symptoms. The objective was to test the hypothesis that treatment with low-dose risperidone results in ‘limbic selective’ D2/D3receptor blockadein vivo.Dynamic single photon emission tomography (SPET) sequences were obtained over 5 hours after injection of [123I]-epidepride (∼150 MBq), using a high-resolution triple-headed brain scanner (Marconi Prism 3000XP). Kinetic modelling was performed using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a normal volunteer control group (n = 5). Six patients treated with low-dose risperidone (mean = 2.6 mg) showed moderate levels of D2/D3occupancy in striatum (49.9%), but higher levels of D2/D3occupancy in thalamus (70.8%) and temporal cortex (75.2%). Occupancy values in striatum were significantly different from thalamus (F (1,4) = 26.3, p < 0.01) and from temporal cortex (F (1,4) = 53.4, p < 0.01). This is the first study to evaluate striatal and extrastriatal occupancy of risperidone. Low dose treatment with risperidone achieves a similar selectivity of limbic cortical over striatal D2/D3receptor blockade to that of atypical antipsychotics with lower D2/D3affinity such as clozapine, olanzapine and quetiapine. This finding is consistent with the relevance of ‘limbic selective’ D2/D3receptor occupancy to the therapeutic efficacy of atypical antipsychotic drugs.
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