D2 receptor occupancy during high- and low-dose therapy with the atypical antipsychotic amisulpride: a 123I-iodobenzamide SPECT study

J Nucl Med. 2005 Jun;46(6):1028-33.

Abstract

Amisulpride appears to be an effective agent for treating positive or negative symptoms of schizophrenia, depending on dose. The aim of this study was to assess striatal dopamine D(2) receptor availability by means of (123)I-iodobenzamide (IBZM) SPECT in patients treated with high and low doses of this atypical antipsychotic drug.

Methods: Twenty-nine patients (19 men and 10 women, age range, 19-68 y) with schizophrenia treated with high doses (15 patients; 400-1,200 mg/d; mean dose, 666.7 +/- 219.3 mg/d) or low doses (14 patients; 50-300 mg/d; mean dose, 228.6 +/- 93.5 mg/d) of amisulpride were examined. For assessment of plasma amisulpride concentration, blood samples were taken. Brain SPECT was performed 2 h after intravenous injection of 185 MBq of (123)I-IBZM. For semiquantitative evaluation, transverse slices corrected for attenuation (Chang's first-order method) were used to calculate specific binding in the striatum, with the frontal cortex used as background.

Results: In all patients treated with amisulpride, specific binding of (123)I-IBZM to D(2) receptors was significantly lower (P < 0.001) than in healthy controls (0.95). Both groups treated with amisulpride differed significantly in specific binding of (123)I-IBZM to dopamine D(2) receptors (0.20 vs. 0.31, P < 0.05). D(2) receptor blockade correlated well with the administered dose of amisulpride and with amisulpride plasma concentration.

Conclusion: Our findings suggest that amisulpride treatment leads to a significant occupancy of postsynaptic dopamine D(2) receptors. The blockade of D(2) receptors tends to be significantly lower in patients receiving low-dose amisulpride therapy than in patients receiving high-dose therapy.

MeSH terms

  • Adult
  • Amisulpride
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / therapeutic use*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Iodine Radioisotopes / metabolism
  • Iodobenzenes / metabolism*
  • Male
  • Middle Aged
  • Radiopharmaceuticals / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Sulpiride / administration & dosage
  • Sulpiride / analogs & derivatives*
  • Sulpiride / blood
  • Sulpiride / therapeutic use*
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Antipsychotic Agents
  • Iodine Radioisotopes
  • Iodobenzenes
  • Radiopharmaceuticals
  • Receptors, Dopamine D2
  • idobenzamide
  • Sulpiride
  • Amisulpride