ABSTRACT
PET imaging studies of the role of the dopamine D2 receptor family in movement and neuropsychiatric disorders are limited by the use of radioligands that have near-equal affinities for D2 and D3 receptor subtypes and are susceptible to competition with endogenous dopamine. By contrast, the radioligand [¹8F]N-methylbenperidol ([¹8F]NMB) has high selectivity and affinity for the D2 receptor subtype (D2R) and is not sensitive to endogenous dopamine. Although [¹8F]NMB has high binding levels in striatum, its utility for measuring D2R in extrastriatal regions is unknown. A composite MR-PET image was constructed across 14 healthy adult participants representing average NMB uptake 60 to 120 min after [¹8F]NMB injection. Regional peak radioactivity was identified using a peak-finding algorithm. FreeSurfer and manual tracing identified a priori regions of interest (ROI) on each individual's MR image and tissue activity curves were extracted from coregistered PET images. [¹8F]NMB binding potentials (BP(ND) s) were calculated using the Logan graphical method with cerebellum as reference region. In eight unique participants, extrastriatal BP(ND) estimates were compared between Logan graphical methods and a three-compartment kinetic tracer model. Radioactivity and BP(ND) levels were highest in striatum, lower in extrastriatal subcortical regions, and lowest in cortical regions relative to cerebellum. Age negatively correlated with striatal BP(ND) s. BP(ND) estimates for extrastriatal ROIs were highly correlated across kinetic and graphical methods. Our findings indicate that PET with [¹8F]NMB measures specific binding in extrastriatal regions, making it a viable radioligand to study extrastriatal D2R levels in healthy and diseased states.
Subject(s)
Benperidol/analogs & derivatives , Brain/diagnostic imaging , Positron-Emission Tomography , Receptors, Dopamine D2/metabolism , Adult , Aged , Aged, 80 and over , Benperidol/analysis , Cerebellum/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Corpus Striatum/diagnostic imaging , Dopamine Antagonists/pharmacology , Dopamine D2 Receptor Antagonists , Female , Fluorine Radioisotopes/analysis , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Organ SpecificityABSTRACT
In this study two butyrophenones, droperidol and benperidol were voltammetrically investigated using platinum and specially activated glass carbon electrodes. The behaviours of the substance were investigated in various electrolyte solutions having different pH values and by different scan rates. As a result of the studies it was shown that the quantitative determinations of the substances from their pharmaceutical preparations could be made rapidly and simply without any separation from the excipients.
Subject(s)
Antipsychotic Agents/analysis , Benperidol/analysis , Droperidol/analysis , Electrochemistry , ElectrodesABSTRACT
Laser microprobe mass analysis (LAMMA) was used for the structural characterization of polyfunctional drugs and their oxygenated metabolites, in particular the N-oxides. The spectra usually yield the molecular weight as well as intense fragments. The structural information is characteristically distributed between the positive and negative ions. To rationalize the unfamiliar fragmentation, tentative pathways are introduced. Key elements are the formation of odd-electron molecular (and fragment) ions, the correlation between cations and anions, as well as the three-dimensional representation of structures. The combination of mild desorption and abundant fragmentation makes LAMMA a valuable tool in the study of N-oxides.
