• Corpus ID: 29518485

S33084, a novel, potent, selective, and competitive antagonist at dopamine D(3)-receptors: I. Receptorial, electrophysiological and neurochemical profile compared with GR218,231 and L741,626.

@article{Millan2000S33084AN,
  title={S33084, a novel, potent, selective, and competitive antagonist at dopamine D(3)-receptors: I. Receptorial, electrophysiological and neurochemical profile compared with GR218,231 and L741,626.},
  author={Mark J Millan and Alain P. Gobert and Adrian Newman-Tancredi and Françoise Lejeune and Didier Cussac and Jean Michel Rivet and Valérie Audinot and Thierry Dubuffet and Gilbert Lavielle},
  journal={The Journal of pharmacology and experimental therapeutics},
  year={2000},
  volume={293 3},
  pages={
          1048-62
        }
}
The benzopyranopyrrole S33084 displayed pronounced affinity (pK(i) = 9.6) for cloned human hD(3)-receptors, and >100-fold lower affinity for hD(2) and all other receptors (>30) examined. S33084 concentration dependently, potently, and competitively (pA(2) = 9.7) antagonized dopamine (DA)-induced [(35)S]guanosine-5'- O-(3-thio)triphosphate (GTPgammaS) binding at hD(3)-receptors. It also concentration dependently abolished stimulation by DA of hD(3)-receptor-coupled mitogen-activated protein… 
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.
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
TLDR
A novel benzopyranopyrrole, S33084, that behaves as a potent, competitive, and selective (.100-fold) antagonist at cloned, human and native rat D3versus hD2-receptors (Table 1), and which shows only negligible lower affinity for all other sites examined to date.
S32504, a Novel Naphtoxazine Agonist at Dopamine D3/D2 Receptors: I. Cellular, Electrophysiological, and Neurochemical Profile in Comparison with Ropinirole
TLDR
D3/D2 agonist and antiparkinsonian agent ropinirole mimicked the profile of S32504, which is a potent and selective agonist at dopamine D3 and D2 receptors.
Cariprazine (RGH-188), a Dopamine D3 Receptor-Preferring, D3/D2 Dopamine Receptor Antagonist–Partial Agonist Antipsychotic Candidate: In Vitro and Neurochemical Profile
TLDR
The antagonist–partial agonist properties of cariprazine at D3 and D2 receptors, with very high and preferential affinity to D3 receptors, make it a candidate antipsychotic with a unique pharmacological profile among known antipsychotics.
BP 897, a selective dopamine D3 receptor ligand with therapeutic potential for the treatment of cocaine-addiction.
TLDR
These interesting preclinical findings with BP 897 provide additional validation for dopamine D(3) receptor as a therapeutic target for the treatment of cocaine abuse and its associated central nervous system (CNS) disorders.
Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15
TLDR
Neurochemical comparison of RG-15 with antagonists having a different affinity and selectivity toward D3 and D2 receptors indicate that D3 receptors have little, if any, role in the control of presynaptic dopamine biosynthesis/release in dopaminergic terminal regions.
The Tetrahydroisoquinoline Derivative SB269,652 Is an Allosteric Antagonist at Dopamine D3 and D2 Receptors
TLDR
It is shown that the tetrahydroisoquinoline 1H-indole-2-carboxylic acid (SB269,652) behaves as an atypical, allosteric antagonist at D3 and D2 receptors, and Schild analysis using Gαi3 assays, and studies of radioligand association and dissociation kinetics, supported allosterics actions of SB269,653.
acetamide ) , a Preferential Dopamine D 3 versus D 2 Receptor Antagonist and Potential Antipsychotic Agent : III . Actions in Models of Therapeutic Activity and Induction of Side Effects
TLDR
To summarize, reflecting preferential blockade of D3 versus D2 receptors, S33138 preserves and/or enhances cognitive function, increases frontocortical cholinergic transmission, and is active in models of antipsychotic properties at doses well below those inducing catalepsy.
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References

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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.
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
TLDR
A novel benzopyranopyrrole, S33084, that behaves as a potent, competitive, and selective (.100-fold) antagonist at cloned, human and native rat D3versus hD2-receptors (Table 1), and which shows only negligible lower affinity for all other sites examined to date.
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.
Neurochemical and functional characterization of the preferentially selective dopamine D3 agonist PD 128907.
TLDR
Findings indicating that PD 128907 shows a preference for DA D3 over D2L and D4.2 receptors indicates that its action at low doses may be due to interaction with D3 receptors and at higher doses, with both D2 and D 3 receptors.
The preferential dopamine D3 receptor ligand, (+)-UH232, is a partial agonist.
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TLDR
Clear functional effects at different levels of the signaling cascade of hD (2) and hD(3) receptors in CHO cells when expressed at high levels are demonstrated, indicating that hD’s receptors maintain relatively high-affinity agonist binding in the absence of G proteins.
L-745,870, a subtype selective dopamine D4 receptor antagonist, does not exhibit a neuroleptic-like profile in rodent behavioral tests.
TLDR
D dopamine D4 receptor antagonism is not responsible for the ability of clozapine to attenuate amphetamine-induced hyperactivity and conditioned avoidance responding in rodents and the lack of effect of L-745,870 in these behavioral tests is consistent with the inability of the compound to alleviate psychotic symptoms in humans.
Functional correlates of dopamine D3 receptor activation in the rat in vivo and their modulation by the selective antagonist, (+)-S 14297: II. Both D2 and "silent" D3 autoreceptors control synthesis and release in mesolimbic, mesocortical and nigrostriatal pathways.
TLDR
The data suggest that D3 (auto)receptors control synthesis and release of DA in dopaminergic pathways innervating the limbic system, cortex and striatum and that D2/D3 receptor antagonist haloperidol modified DA turnover upon administration alone.
A comparative in vitro and in vivo pharmacological characterization of the novel dopamine D3 receptor antagonists (+)-S 14297, nafadotride, GR 103,691 and U 99194.
TLDR
Both (+)-S 14297 and GR 103,691 are markedly selective ligands that permit the characterization of actions at hD3 vs. hD2 receptors in vitro, but both are of greater utility for the evaluation of their functional significance in vivo.
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