Optimizing limbic selective D2/D3 receptor occupancy by risperidone:: A[123I]-epidepride SPET study

被引:49
作者
Bressan, RA
Erlandsson, K
Jones, HM
Mulligan, RS
Ell, PJ
Pilowsky, LS
机构
[1] Inst Psychiat, Div Psychol Med, Sect Neurochem Imaging, London SE5 8AF, England
[2] UCL, Sch Med, Middlesex Hosp, Inst Nucl Med, London, England
关键词
D O I
10.1097/00004714-200302000-00002
中图分类号
R9 [药学];
学科分类号
1007 ;
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 D-2 receptors, 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' D-2/D-3 receptor blockade in vivo. Dynamic single photon emission tomography (SPET) sequences were obtained over 5 hours after injection of [I-123]-epidepride (similar to150 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 D-2/D-3 occupancy in striatum (49.9%), but higher levels of D-2/D-3 occupancy 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 D-2/D-3 receptor blockade to that of atypical antipsychotics with lower D-2/D-3 affinity such as clozapine, olanzapine and queLiapine. This finding is consistent with the relevance of 'limbic selective' D-2/D-3 receptor occupancy to the therapeutic efficacy of atypical antipsychotic drugs.
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页码:5 / 14
页数:10
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