title: Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum.
abstract: 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. Alpha-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 microM, 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.
authors.affiliation: Clinical Neurochemistry, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Germany. manfred.gerlach@mail.uni-wuerzburg.de
authors.forename: M
authors.initials: M
authors.lastname: Gerlach
authors.forename: K
authors.initials: K
authors.lastname: Double
authors.forename: T
authors.initials: T
authors.lastname: Arzberger
authors.forename: F
authors.initials: F
authors.lastname: Leblhuber
authors.forename: T
authors.initials: T
authors.lastname: Tatschner
authors.forename: P
authors.initials: P
authors.lastname: Riederer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D003342:Corpus Striatum / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3
chemical_list: C493593:DRD3 protein, human; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3