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Decreased striatal dopamine receptor binding in primary focal dystonia: A D2 or D3 defect?

Authors

  • Morvarid Karimi MD,

    Corresponding author
    1. Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA
    • Department of Neurology, Washington University School of Medicine, 660 S. Euclid, Campus Box 8111, St. Louis, MO 63110-1093
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  • Stephen M. Moerlein Pharm D, PhD,

    1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA
    2. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, Missouri, USA
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  • Tom O. Videen, PhD,

    1. Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA
    2. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA
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  • Robert R. Luedtke PhD,

    1. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA
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  • Michelle Taylor BS,

    1. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA
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  • Robert H. Mach PhD,

    1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA
    2. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, Missouri, USA
    3. Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, Missouri, USA
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  • Joel S. Perlmutter MD

    1. Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA
    2. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA
    3. Department of Neurobiology, Washington University School of Medicine, Saint Louis, Missouri, USA
    4. Department of Occupational Therapy, Washington University School of Medicine, Saint Louis, Missouri, USA
    5. Department of Physical Therapy, Washington University School of Medicine, Saint Louis, Missouri, USA
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  • Potential conflict of interest: M. Karimi has received a 1-year fellowship from Allergan.

Abstract

Dystonia is an involuntary movement disorder characterized by repetitive patterned or sustained muscle contractions causing twisting or abnormal postures. Several lines of evidence suggest that abnormalities of dopaminergic pathways contribute to the pathophysiology of dystonia. In particular, dysfunction of D2-like receptors that mediate function of the indirect pathway in the basal ganglia may play a key role. We have demonstrated with positron emission tomography that patients with primary focal cranial or hand dystonia have reduced putamenal specific binding of [18F]spiperone, a nonselective D2-like radioligand with nearly equal affinity for serotonergic 5-HT(2A) sites. We then repeated the study with [18F]N-methyl-benperidol (NMB), a more selective D2-like receptor radioligand with minimal affinity for 5-HT(2A). Surprisingly, there was no decrease in NMB binding in the putamen of subjects with dystonia. Our findings excluded reductions of putamenal uptake greater than 20% with 95% confidence intervals. The analysis of the in vitro selectivity of NMB and spiperone demonstrated that NMB was highly selective for D2 receptors relative to D3 receptors (200-fold difference in affinity), whereas spiperone has similar affinity for all three of the D2-like receptor subtypes. These findings when coupled with other literature suggest that a defect in D3, rather than D2, receptor expression may be associated with primary focal dystonia. © 2010 Movement Disorder Society.

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