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

TY - JOUR

T1 - Optimizing limbic selective D2/D3 receptor occupancy by risperidone: A[I-123]-epidepride SPET study

AU - Bressan, R A

AU - Erlandsson, K

AU - Jones, H M

AU - Mulligan, R S

AU - Ell, P J

AU - Pilowsky, L S

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

M3 - Conference paper

VL - 23

SP - 5

EP - 14

JO - Journal of Clinical Psychopharmacology

JF - Journal of Clinical Psychopharmacology

IS - 1

T2 - Annual Meeting of the European-Association-of-Nuclear-Medicine

Y2 - 1 January 2003

ER -