ArticleEuropean neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology2009
Comparison of the enantiomers of (+/-)-doxanthrine, a high efficacy full dopamine D(1) receptor agonist, and a reversal of enantioselectivity at D(1) versus alpha(2C) adrenergic receptors.
Article in European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
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- Reward learning as a potential target for pharmacological augmentation of cognitive remediation for schizophrenia: a roadmap for preclinical development.Frontiers in neuroscience · 2013Article
- Comparison of the D₁ dopamine full agonists, dihydrexidine and doxanthrine, in the 6-OHDA rat model of Parkinson's disease.Psychopharmacology · 2012Article
- Ligand-specific roles for transmembrane 5 serine residues in the binding and efficacy of dopamine D(1) receptor catechol agonists.Molecular pharmacology · 2012Article
- D₁ receptor activation improves vigilance in rats as measured by the 5-choice continuous performance test.Psychopharmacology · 2012Article
- A "genome-to-lead" approach for insecticide discovery: pharmacological characterization and screening of Aedes aegypti D(1)-like dopamine receptors.PLoS neglected tropical diseases · 2012Article
- Facile synthesis of octahydrobenzo[h]isoquinolines: novel and highly potent D1 dopamine agonists.Bioorganic & medicinal chemistry · 2010Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Parkinson's disease is a neurodegenerative condition involving the death of dopaminergic neurons in the substantia nigra. Dopamine D(1) receptor agonists are potential alternative treatments to current therapies that employ L-DOPA, a dopamine precursor. We evaluated the pharmacological profiles of the enantiomers of a novel dopamine D(1) receptor full agonist, doxanthrine (DOX) at D(1) and alpha(2C) adrenergic receptors. (+)-DOX displayed greater potency and intrinsic activity than (-)-DOX in porcine striatal tissue and in a heterologous D(1) receptor expression system. Studies in MCF7 cells, which express an endogenous human dopamine D(1)-like receptor, revealed that (-)-DOX was a weak partial agonist/antagonist that reduced the functional activity of (+)-DOX and dopamine. (-)-DOX had 10-fold greater potency than (+)-DOX at alpha(2C) adrenergic receptors, with an EC50 value of 4 nM. These findings demonstrate a reversed stereoselectivity for the enantiomers of DOX at D(1) and alpha(2C) receptors and have implications for the therapeutic utility of doxanthrine.
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