title: High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia.
abstract: The 'atypicality' of the antipsychotic drug, amisulpride, has been attributed to preferential extrastriatal binding. Previous investigations of striatal D2 receptor occupancy by amisulpride revealed conflicting results. The aim of this PET study was to measure the striatal occupancy by amisulpride and to correlate it with the corresponding drug plasma concentrations. Nine amisulpride-treated patients and 12 healthy volunteers serving as controls were studied with PET and [18F]desmethoxyfallypride. Occupancy values and plasma concentrations were nonlinearly fitted to an E max model. Results showed 43-85% (putamen) and 67-90% (caudate) D2-like receptor occupancy. Plasma amisulpride concentrations at the time of tracer injection, but not administered doses, were significantly nonlinearly correlated to occupancy levels (putamen: rS=0.88, p=0.0017; caudate: r S=0.78, p=0.0127). Calculated Emax was similar in both caudate and putamen, but occupancy levels were lower in caudate at lower amisulpride plasma concentrations. Calculated plasma levels to attain 60-80% receptor occupancy ranged from 119 to 474 ng/ml (caudate) and from 241 to 732 ng/ml (putamen). This reveals a broad range of plasma concentrations producing less than 80% striatal receptor occupancy. However, our data show high striatal D2-like receptor occupancies under rising plasma concentrations. Using the full range of recommended amisulpride dosage, striatal occupancies up to 90% can be measured.
authors.affiliation: Department of Psychiatry, University of Mainz, Mainz, Germany. vernalek@mail.uni-mainz.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
authors.forename: Thomas
authors.initials: T
authors.lastname: Siessmeier
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Härtter
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.forename: Peter
authors.initials: P
authors.lastname: Stoeter
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
mesh_terms: D000328:Adult; D000465:Algorithms; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012457:Salicylamides; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
chemical_list: D014150:Antipsychotic Agents; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C100958:desmethoxyfallypride; D013469:Sulpiride; D000077582:Amisulpride