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

Rodrigo A Bressan·Kjell Erlandsson·Hugh M Jones·Rachel S Mulligan·Peter J Ell·Lyn S Pilowsky
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Abstract

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 D2 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' D2/D3 receptor blockade in vivo. Dynamic single photon emission tomography (SPET) sequences were obtained over 5 hours after injection of [123I]-epidepride (approximately 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/D3 occupancy in striatum (49.9%), but higher levels of D2/D3 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 D2/D3 receptor blockade to that of atypical antipsychotics with lower D2/D3 affinity such as clozapine, olanzapine and quetiapine. This finding is consistent with the relevance of 'limbic selective' D2/D3 receptor occupancy to the therapeutic efficacy of atypical antipsychotic drugs.

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AdultAlgorithmsAntipsychotic AgentsBenzamidesFemaleHumansImage Processing, Computer-AssistedLimbic SystemMalePyrrolidinesRadiopharmaceuticalsReceptors, Dopamine D2Receptors, Dopamine D3RisperidoneSchizophreniaTomography, Emission-Computed, Single-PhotonClinical TrialJournal ArticleResearch Support, Non-U.S. Gov't

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BibTeXRIS

Rodrigo A Bressan, Kjell Erlandsson, Hugh M Jones, Rachel S Mulligan, Peter J Ell, Lyn S Pilowsky. 2003. Optimizing limbic selective D2/D3 receptor occupancy by risperidone: a [123I]-epidepride SPET study.. https://doi.org/10.1097/00004714-200302000-00002

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