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

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Bressan RA, Erlandsson K, Jones HM, Mulligan RS, Ell PJ, Pilowsky LS

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

J Clin Psychopharmacol. 2003 Feb;23(1):5-14. doi: 10.1097/00004714-200302000-00002.

PubMed ID

12544369 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Quetiapine	Dopamine D3 receptor	Protein	Humans	Unknown	Ligand	Details