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.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Antipsychotic Agents / pharmacokinetics*
  • Antipsychotic Agents / pharmacology*
  • Benzamides* / chemical synthesis
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Limbic System / diagnostic imaging*
  • Limbic System / metabolism*
  • Male
  • Pyrrolidines* / chemical synthesis
  • Radiopharmaceuticals* / chemical synthesis
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3
  • Risperidone / pharmacokinetics*
  • Risperidone / pharmacology*
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Antipsychotic Agents
  • Benzamides
  • DRD3 protein, human
  • Pyrrolidines
  • Radiopharmaceuticals
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • epidepride
  • Risperidone