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

@article{NewmanTancredi2002DifferentialAO,
  title={Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and $\alpha$1/$\alpha$2-Adrenoceptor},
  author={Adrian Newman-Tancredi and Didier Cussac and Valérie Audinot and Jean Paul Nicolas and Fr{\'e}d{\'e}ric De Ceuninck and Jean A. Boutin and Mark J Millan},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2002},
  volume={303},
  pages={805 - 814}
}
The accompanying multivariate analysis of the binding profiles of antiparkinson agents revealed contrasting patterns of affinities at diverse classes of monoaminergic receptor. Herein, we characterized efficacies at human (h)D2SHORT(S), hD2LONG(L), hD3, and hD4.4receptors and at hα2A-, hα2B-, hα2C-, and hα1A-adrenoceptors (ARs). As determined by guanosine 5′-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding, no ligand displayed “full” efficacy relative to dopamine (100%) at all “D2-like” sites… 
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.
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
TLDR
An innovative multivariate analysis revealed marked heterogeneity in binding profiles of antiparkinson agents at diverse receptors implicated in the etiology and/or treatment of Parkinson's disease.
Pharmacological Profile of 2-Bromoterguride at Human Dopamine D2, Porcine Serotonin 5-Hydroxytryptamine 2A, and α2C-Adrenergic Receptors, and Its Antipsychotic-Like Effects in Rats
TLDR
2-bromoterguride may be a strong candidate for the treatment of schizophrenia with a lower risk to induce EPS because of its in vitro and in vivo properties.
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.
Differential induction of adenylyl cyclase supersensitivity by antiparkinson drugs acting as agonists at dopamine D1/D2/D3 receptors vs D2/D3 receptors only: Parallel observations from co-transfected human and native cerebral receptors
TLDR
AC supersensitivity is elicited by the sustained exposure of cloned human and native mouse populations of dopaminergic receptors, to D(2/D(3) but not D(1)/D(2)/D (3) agonists, which may be related to the exacerbation of gambling in Parkinson's disease that is provoked by antiparkinson agents acting as selective D( 2)/D3) receptor agonists.
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.
Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole
TLDR
It is demonstrated that S32504 robustly, concentration-dependently and completely protects terminally differentiated SH-SY5Y cells against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in vitro, and robustly protects dopaminergic neurones against the neurotoxic effects of MPP(+) and MPTP in in vitro and in vivo models, respectively.
S32504, a Novel Naphtoxazine Agonist at Dopamine D3/D2 Receptors: II. Actions in Rodent, Primate, and Cellular Models of Antiparkinsonian Activity in Comparison to Ropinirole
TLDR
S32504 displays potent and stereospecific activity in rodent, primate, and cellular models of antiparkinsonian properties and engagement of D3 receptors contributes to its neuroprotective properties.
Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors
The dopamine D2/D3 receptor agonist and &agr;2 adrenergic receptor antagonist, piribedil, is used clinically as monotherapy and as an adjunct to L-3,4-dihydroxyphenylalanine in the treatment of
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.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 50 REFERENCES
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
TLDR
An innovative multivariate analysis revealed marked heterogeneity in binding profiles of antiparkinson agents at diverse receptors implicated in the etiology and/or treatment of Parkinson's disease.
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.
Functional correlates of dopamine D3 receptor activation in the rat in vivo and their modulation by the selective antagonist, (+)-S 14297: 1. Activation of postsynaptic D3 receptors mediates hypothermia, whereas blockade of D2 receptors elicits prolactin secretion and catalepsy.
TLDR
Data demonstrate that the novel naphthofurane, (+)-S 14297, is a selective ligand (antagonist) at dopamine D3 receptors and suggest that their activation mediates hypothermia in the rat.
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.
Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D1, D2 and D3 receptors.
TLDR
The results suggest that the activity of recently developed antiparkinsonian drugs at either the dopamine D1 or the serotonin D3 and not only the dopamineD2 receptors should be taken into account in analyses of their mechanisms of action in therapeutics.
S18616, a highly potent spiroimidazoline agonist at alpha(2)-adrenoceptors: II. Influence on monoaminergic transmission, motor function, and anxiety in comparison with dexmedetomidine and clonidine.
TLDR
Through activation of alpha(2)-ARs, S18616 potently inhibits corticolimbic adrenergic, serotonergic, and (frontocortical) dopaminergic transmission in parallel with the expression of its anxiolytic and sedative properties.
Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra
TLDR
The present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D2, but not D3 or D4, receptor-mediated G-protein activation.
Characterization of dopaminergic compounds at hD2short, hD4.2 and hD4.7 receptors in agonist-stimulated [35S]GTPγS binding assays
TLDR
It is suggested that therapeutic distinctions between typical and atypical antipsychotic drugs cannot be made based on their function at D2short, D4.2 and D 4.7 subtypes of dopamine receptors.
Agonist action at D2(long) dopamine receptors: ligand binding and functional assays
TLDR
There was no clear relation betwen the ability of an agonist to stabilize the formation of the ternary complex of agonist/receptor/G‐protein and the maximal activity of the agonist or the amplification factor.
...
1
2
3
4
5
...