Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes

@article{Millan2002DifferentialAO,
  title={Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes},
  author={Mark J Millan and Lisa Maiofiss and Didier Cussac and Valérie Audinot and Jean A. Boutin and Adrian Newman-Tancredi},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2002},
  volume={303},
  pages={791 - 804}
}
Because little comparative information is available concerning receptor profiles of antiparkinson drugs, affinities of 14 agents were determined at diverse receptors implicated in the etiology and/or treatment of Parkinson's disease: human (h)D1, hD2S, hD2L, hD3, hD4, and hD5 receptors; human 5-hydroxytryptamine (5-HT)1A, h5-HT1B, h5-HT1D, h5-HT2A, h5-HT2B, and h5-HT2Creceptors; hα1A-, hα1B-, hα1D-, hα2A-, hα2B-, hα2C-, rat α2D-, hβ1-, and hβ2-adrenoceptors (ARs); and native histamine1… 
Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor
TLDR
In conclusion, antiparkinson agents display diverse agonist and antagonist properties at multiple subtypes of D2-like receptor and α1/α2-AR, actions, which likely contribute to their contrasting functional profiles.
Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. III. Agonist and Antagonist Properties at Serotonin, 5-HT1 and 5-HT2, Receptor Subtypes
TLDR
Antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes, although all show modest (agonist) activity at5-HT1A sites, and their contrasting actions at 5-ht2A and 5- HT2C sites may be of particular significance to their functional profiles in vivo.
S32212, a Novel Serotonin Type 2C Receptor Inverse Agonist/α2-Adrenoceptor Antagonist and Potential Antidepressant: I. A Mechanistic Characterization
TLDR
S32212 behaves as an inverse agonist at h5-HT2C receptors and as an antagonist at human α2-adrenoceptors (and h5/HT2A receptors), potentially relevant to the treatment of depression.
α2-Adrenoceptors are targets for antipsychotic drugs
TLDR
It is concluded that α2-adrenoceptors may be promising targets in the antipsychotic therapy.
Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.
TLDR
Results show that methiothepin, ketanserin, clozapine, lisuride and buspirone can block alpha1-adrenoceptors in the rat systemic vasculature.
Involvement of dopamine D2/D3 receptors and BDNF in the neuroprotective effects of S32504 and pramipexole against 1-methyl-4-phenylpyridinium in terminally differentiated SH-SY5Y cells
TLDR
S32504 and, less potently, pramipexole show robust, stereospecific, and long-lasting neuroprotective effects against MPP + toxicity that involve D 3 receptors that reflect downstream recruitment of BDNF and via a PK3-AKT pathway.
Dopamine heteroreceptor complexes as therapeutic targets in Parkinson’s disease
TLDR
The hypothesis is given that changes in the function of the dopamine heteroreceptor complexes may help to understand the molecular mechanisms underlying the motor complications of long-term therapy in Parkinson’s disease (PD) with l-DOPA and dopamine receptor agonists.
Discriminative stimulus properties of S32504, a novel D3/D2 receptor agonist and antiparkinson agent, in rats: attenuation by the antipsychotics, aripiprazole, bifeprunox, N-desmethylclozapine, and by selective antagonists at dopamine D2 but not D3 receptors
TLDR
The antiparkinson agent, S32504, displays DS properties principally mediated by high-efficacy activation of D2 receptors Antipsychotics known to act as partial agonists at D2/D3 receptors attenuate DS properties of S32 504, actions reflecting their low efficacy at these sites.
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.
From the cell to the clinic: a comparative review of the partial D₂/D₃receptor agonist and α2-adrenoceptor antagonist, piribedil, in the treatment of Parkinson's disease.
  • M. Millan
  • Medicine, Biology
    Pharmacology & therapeutics
  • 2010
TLDR
This paper focuses on the distinctive cellular, preclinical and therapeutic profile of piribedil, comparisons to pramipexole, ropinirole and pergolide, and the core triad of symptoms that characterises PD-motor dysfunction, depressed mood and cognitive impairment.
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References

SHOWING 1-10 OF 76 REFERENCES
Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor
TLDR
In conclusion, antiparkinson agents display diverse agonist and antagonist properties at multiple subtypes of D2-like receptor and α1/α2-AR, actions, which likely contribute to their contrasting functional profiles.
Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. III. Agonist and Antagonist Properties at Serotonin, 5-HT1 and 5-HT2, Receptor Subtypes
TLDR
Antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes, although all show modest (agonist) activity at5-HT1A sites, and their contrasting actions at 5-ht2A and 5- HT2C sites may be of particular significance to their functional profiles in vivo.
Actions of roxindole at recombinant human dopamine D2, D3 and D4 and serotonin 5-HT1A, 5-HT1B and 5-HT1D receptors
TLDR
The present data suggest that roxindole activates mainly D3 vs. D2 or D4 receptors and 5-HT1A vs. 5- HT1B or 5,HT1D receptors, and Activation of D3 and/or 5-ht1A receptors may contribute to its potential antidepressant properties.
S33084, a novel, potent, selective, and competitive antagonist at dopamine D(3)-receptors: II. Functional and behavioral profile compared with GR218,231 and L741,626.
TLDR
D(2)-receptors are principally involved in these paradigms, although D(3)-receptionors may contribute to induction of hypothermia and PEs, and S33084 was inactive in models of potential antipsychotic and extrapyramidal activity and failed to modify spontaneous locomotor behavior.
The "selective" dopamine D1 receptor antagonist, SCH23390, is a potent and high efficacy agonist at cloned human serotonin2C receptors
TLDR
SCH23390 is a potent and high efficacy agonist at h5-HT2C receptors and may contribute to its functional properties both in animals and in humans.
S 33084 , a Novel , Potent , Selective , and Competitive Antagonist at Dopamine D 3-Receptors : II . Functional and Behavioral Profile Compared with GR 218 , 231 and L 741 , 626
The selective dopamine D3-receptor antagonist S33084 dose dependently attenuated induction of hypothermia by 7-hydroxy-2-dipropylaminotetralin (7-OH-DPAT) and PD128,907. S33084 also dose dependently
Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha(2)-adrenoceptors: cellular and functional characterization.
TLDR
The antiparkinsonian agent piribedil displays essentially antagonist properties at cloned, human and cerebral, rat alpha(2)-ARs and weakly induced mitogen-activated protein kinase phosphorylation via wild-type halpha(2A-ARs, although attenuating its phosphorylated by NE.
Selectivity of some ergot derivatives for 5-HT1 and 5-HT2 receptors of rat cerebral cortex.
TLDR
Overall, the ergot derivatives displayed markedly different affinities and selectivities for central 5-HT receptors suggesting that their serotonergic actions should be considered when evaluating their pharmacological spectrum of activity.
Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors.
TLDR
The dopamine D3 receptor selectivity of pramipexole may explain the previously described properties of this drug, including its potent autoreceptor preference, while quinpirole and bromocriptine are non-selective or more D2/D4 receptor selective.
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.
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