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

Article Details

Citation

Gerlach M, Double K, Arzberger T, Leblhuber F, Tatschner T, Riederer P

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

J Neural Transm (Vienna). 2003 Oct;110(10):1119-27. doi: 10.1007/s00702-003-0027-5.

PubMed ID
14523624 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Dihydro-alpha-ergocryptineD(1) dopamine receptor (Protein Group)Protein groupHumans
Yes
Partial agonist
Details
Dihydro-alpha-ergocryptineDopamine D2 receptorProteinHumans
Yes
Agonist
Details
Dihydro-alpha-ergocryptineDopamine D3 receptorProteinHumans
Yes
Partial agonist
Details