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

@article{Gerlach2003DopamineRA,
  title={Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum},
  author={Manfred Gerlach and Kay L. Double and Thomas Arzberger and Friedrich Leblhuber and Thomas Tatschner and Peter Franz Riederer},
  journal={Journal of Neural Transmission},
  year={2003},
  volume={110},
  pages={1119-1127}
}
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… 

Tables from this paper

Dopamine D1 receptor ligands: Where are we now and where are we going
TLDR
A number of D1 receptor agonists with full intrinsic activity, including A‐86929 (31a), dinapsoline (32a, dinoxyline (34a), and doxanthrine (35a) were identified, but the fate of such ligands for clinical use as treatments of Parkinson's disease and other related CNS disorders is not optimistic.
Dopamine D 1 Receptor Ligands: Where AreWe Now and Where AreWe Going
TLDR
A renewed interest was ignited in the early 1990s by Nichols and Mailman who developed dihydrexidine (27a), the first high affinity full efficacy agonist for the D1 receptor, but the fate of such ligands for clinical use as treatments of Parkinson's disease and other related CNS disorders is not optimistic since the clinical trial was not successful.
Antiparkinson therapeutic potencies correlate with their affinities at dopamine D2High receptors
TLDR
D2High is the primary and common target for the antiparkinson action of dopamine agonists, and there was a clear correlation between the Ki values at D2High and their therapeutic concentrations in the plasma water, as derived from the known concentrations after correction for the fraction bound to the human plasma proteins.
Targeting the dopamine D3 receptor: an overview of drug design strategies
TLDR
This review summarizes the functional and pharmacological characteristics of D3Rs, including the design and clinical relevance of full agonists, partial agonists and antagonists, as well as the capacity of these receptors to form active homodimer, heterodimers or higher order receptor complexes as pharmacological targets in several neurological and neurodegenerative disorders.
Dopamine receptor agonists for Parkinson's disease
TLDR
This review summarizes pre-clinical and clinical data on second-generation, first-line non-ergolinic DA agonists and their motor, non-motor and putative neuroprotective effects and addressed the anti-parkinsonian potential of recently developedDA agonists that reached Phase II and III clinical trials.
The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson’s disease
TLDR
Rotigotine can be characterized as a specific dopamine receptor agonist with a preference for the D3 receptor over D2 and D1 receptors in Parkinson's disease and possible other indications such as restless legs syndrome.
[A current view on dopamine receptor agonists in the treatment of Parkinson's disease].
  • N. Titova
  • Medicine, Psychology
    Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
  • 2015
TLDR
Dopamine receptor agonists (DRA) is a widely used group of antiparkinsonian drugs and has demonstrated an important role in the treatment of Parkinson's disease, with a good control of motor symptoms and the possibility of monotherapy in the early stages of disease.
[A current view on dopamine receptor agonists in the treatment of Parkinson's disease].
TLDR
Dopamine receptor agonists (DRA) is a widely used group of antiparkinsonian drugs and has demonstrated an important role in the treatment of Parkinson's disease, with a good control of motor symptoms and the possibility of monotherapy in the early stages of disease.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 33 REFERENCES
Dopamine D3 Receptors
TLDR
Until agonists with greater selectivity and specificity at D3 receptors can be developed, however, it will be difficult to determine if a D3 receptor agonist would possess a higher TI than the drugs currently available for the treatment of Parkinson’s disease.
Dopamine receptor agonists: selectivity and dopamine D1 receptor efficacy.
Dopamine D1 Receptor Agonists
TLDR
The potential value of the newly developed D1 receptor agonists in the treatment of Parkinson’s disease seems limited, as several of these compounds lose their efficacy in stimulating motor behaviour upon sustained administration and induce dyskinetic behaviour.
Dopamine Receptors: Novel Insights from Biochemical and Genetic Studies
TLDR
Results of studies that suggest that these receptor proteins are expressed in monomeric and oligomeric forms are summarized and results of a growing number of gene-targeting studies that begin to illustrate major differences in the phenotypes of D1-, D2-, and D3-mutant mice are reviewed.
Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors.
Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist
Comparative Review of Dopamine Receptor Agonists in Parkinson’s Disease
SummaryLimitations of long term levodopa therapy for Parkinson’s disease represent a major problem in the management of many patients. Dopamine receptor agonists provide antiparkinsonian effects and
Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells
TLDR
The results show that ropinirole is a full agonist at human D2, D3 and D4 dopamine receptors, and at least 10 fold selective for the human dopamine D3 receptor over the other D2 receptor family members.
Dopamine receptors and brain function
...
1
2
3
4
...