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

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 (K_i=35.4 and 56.7 nM, respectively) for D₁ receptors, than the D₁/D₂ dopamine agonist pergolide (K_i=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 (K_i=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 (K_i=79.5 and 98.7 µM, respectively using [³H]spiperone). Interestingly we also found that the affinities of cabergoline (K_i=1.27 nM), lisuride (K_i=1.08 nM) and pergolide (K_i=0.86 nM) for the D₃ receptor subtype were comparable to that of pramipexole (K_i=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.