Differential profile of typical, atypical and third generation antipsychotics at human 5-HT7a receptors coupled to adenylyl cyclase: detection of agonist and inverse agonist properties

@article{RaulyLestienne2007DifferentialPO,
  title={Differential profile of typical, atypical and third generation antipsychotics at human 5-HT7a receptors coupled to adenylyl cyclase: detection of agonist and inverse agonist properties},
  author={Isabelle Rauly-Lestienne and Elisa Boutet-Robinet and Marie-Christine Ailhaud and Adrian Newman-Tancredi and Didier Cussac},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={2007},
  volume={376},
  pages={93-105}
}
Abstract5-HT7 receptors are present in thalamus and limbic structures, and a possible role of these receptors in the pathology of schizophrenia has been evoked. In this study, we examined binding affinity and agonist/antagonist/inverse agonist properties at these receptors of a large series of antipsychotics, i.e., typical, atypical, and third generation compounds preferentially targeting D2 and 5-HT1A sites. Adenylyl cyclase (AC) activity was measured in HEK293 cells stably expressing the… Expand
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References

SHOWING 1-10 OF 83 REFERENCES
Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia.
TLDR
The data indicate that aripiprazole has low efficacy and modest affinity at 5-HT1A receptors, whereas bifeprunox has low affinity but high efficacy, and SSR181507 has intermediate efficacy but high affinity, and is likely to have more prominent 5- HT1A receptor agonist properties. Expand
Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats
TLDR
It is demonstrated that some putative antipsychotics with pronounced 5-HT1A agonists activity, coupled with partial agonist activity at DA D2 receptors, markedly diminish PPI of the startle reflex in rats, raising the issue of the influence of such compounds on sensorimotor gating in humans. Expand
Novel antipsychotic agents with 5-HT1A agonist properties: Role of 5-HT1A receptor activation in attenuation of catalepsy induction in rats
TLDR
Data show that 5-HT(1A) receptor activation reduces the cataleptogenic potential of novel antipsychotic agents but indicate marked diversity in the contribution of 5- HT( 1A) and/or other mechanisms to the profiles of the drugs. Expand
Differential profile of antipsychotics at serotonin 5-HT1A and dopamine D2S receptors coupled to extracellular signal-regulated kinase.
TLDR
Ant antipsychotics display varying efficacies at serotonin 5-HT1A and dopamine D2S receptors which may play a major role in their differential functional profiles in blocking the diverse symptoms of schizophrenia. Expand
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.
TLDR
The authors examined the affinities of 36 typical and atypical antipsychotic agents for the cloned rat 5-hydroxytryptamine-6 and rat5-HT7 receptors in transiently expressed COS-7 cells or stably transfected HEK-293 cells to identify those with high affinity for the newly discovered 5-HT6 receptor. Expand
Antipsychotic-Like vs Cataleptogenic Actions in Mice of Novel Antipsychotics Having D2 Antagonist and 5-HT1A Agonist Properties
TLDR
It is confirmed that 5-HT1A receptor activation reduces or even completely prevents the cataleptogenic potential of novel antipsychotic agents and indicates that the balance of affinity and/or efficacy between D2 and 5- HT1A receptors profoundly influences their pharmacological activities, and will likely impact their therapeutic profiles. Expand
Effects of SB-269970, a 5-HT7 receptor antagonist, in mouse models predictive of antipsychotic-like activity
TLDR
Results indicate that blockade of 5-HT7 receptors partially modulates glutamatergic and dopaminergic function and could be clinically useful for the treatment of positive symptoms of schizophrenia. Expand
5-HT1A receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex
Background: Ziprasidone (Zeldox) is a novel antipsychotic with a unique combination of antagonist activities at monoaminergic receptors and transporters and potent agonist activity at serotoninExpand
Serotonin receptors : their key role in drugs to treat schizophrenia
TLDR
5-HT has joined DA as a critical target for developing effective APDs and led to the search for novel drugs with complex pharmacology, ending the exclusive search for single-receptor targets. Expand
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs
TLDR
The inverse agonist mechanism-of-action of the atypical antipsychotic drugs at the h5HT7 receptors may be different from the typical antipsychotics drugs as these drugs displayed far higher potencies as inverse agonists at the H5 HT7 receptor. Expand
...
1
2
3
4
5
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