Advertisement

Journal of Neural Transmission

, Volume 110, Issue 10, pp 1119–1127 | Cite as

Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum

  • M. Gerlach
  • K. Double
  • T. Arzberger
  • F. Leblhuber
  • T. Tatschner
  • P. Riederer

Summary.

 The aim of this study was to compare dopamine receptor binding affinities of all currently approved dopamine receptor agonist treatments for Parkinson’s disease (PD) in human brain tissue. α-Dihydroergocryptine and lisuride displayed higher comparative affinities (Ki=35.4 and 56.7 nM, respectively) for D1 receptors, than the D1/D2 dopamine agonist pergolide (Ki=447 nM). The second generation non-ergot dopamine receptors agonists pramipexole and ropinirole demonstrated no affinity for D1 receptors at concentrations up to 10−4 M. The ergoline dopamine agonists cabergoline and lisuride displayed the highest affinities for the D2 receptor (Ki=0.61 and 0.95 nM, respectively). Surprisingly, the second generation non-ergot dopamine receptors agonists pramipexole and ropinirole only weakly inhibited binding to D2 receptors (Ki=79.5 and 98.7 µM, respectively using [3H]spiperone). Interestingly we also found that the affinities of cabergoline (Ki=1.27 nM), lisuride (Ki=1.08 nM) and pergolide (Ki=0.86 nM) for the D3 receptor subtype were comparable to that of pramipexole (Ki=0.97 nM). The present results thus support the hypothesis that the antiparkinsonian effect of dopamine receptor agonists is mediated by a more complex interactions with dopamine receptor subtypes than currently believed.

Keywords: Dopamine receptor agonists, dopamine D1-agonist, dopamine D2-agonist, dopamine D3-agonist, Parkinson therapy, dopamine receptors, receptor binding. 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag/Wien 2003

Authors and Affiliations

  • M. Gerlach
    • 1
  • K. Double
    • 2
    • 3
  • T. Arzberger
    • 4
  • F. Leblhuber
    • 5
  • T. Tatschner
    • 6
  • P. Riederer
    • 2
  1. 1.Clinical Neurochemistry, Department of Child and Adolescent Psychiatry and Psychotherapy, Würzburg, GermanyDE
  2. 2.Clinical Neurochemistry, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanyDE
  3. 3.Prince of Wales Medical Research Institute and the University of New South Wales, Sydney, AustraliaAU
  4. 4.Neuropathology, Institute of Pathology, University of Würzburg, Würzburg, GermanyDE
  5. 5.Department of Gerontology, Landesnervenkrankenhaus Wagner-Jauregg, Linz, AustriaAT
  6. 6.Institute for Forensic Medicine, University of Würzburg, Würzburg, GermanyDE

Personalised recommendations