Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies

@article{Stark2006InteractionOT,
  title={Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies},
  author={Arlene D. Stark and Shaun Jordan and Kelly Ann Allers and Robert L. Bertekap and Ruoyan Chen and Tanaz Mistry Kannan and Thaddeus F. P. Molski and Frank D. Yocca and Trevor Sharp and Tetsuro Kikuchi and Kevin D. Burris},
  journal={Psychopharmacology},
  year={2006},
  volume={190},
  pages={373-382}
}
BackgroundAripiprazole (7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2(1H)-quinolinone) is a novel antipsychotic with a mechanism of action that differs from current typical and atypical antipsychotics. Aripiprazole interacts with a range of receptors, including serotonin [5-hydroxytryptamine (5-HT)] and dopamine receptors.Materials and methodsThis study examined aripiprazole’s interactions with 5-HT systems in vitro and in vivo to further clarify its pharmacologic properties… 

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References

SHOWING 1-10 OF 42 REFERENCES

Short communication The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT 1A receptor

TLDR
Aripiprazole is the first dopamine–serotonin system stabilizer, according to a study demonstrating potent, partial agonism at 5-HT1A receptors in a guanosine-5VO-(3-[35 S]thio)-triphosphate ([ 35 S]GTPgS)-binding assay.

The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor.

Effects of the novel antipsychotic agent 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro -2(1H)-quinolinone (OPC-14597) on prolactin release from the rat anterior pituitary gland.

TLDR
The results suggest that OPC-14597 has a mixed agonist/antagonist profile at D2 receptors on lactotroph cells and thereby exerts either an antagonistic or an agonistic action, depending on the preexisting tone of the dopaminergic neuronal activities.

Receptor reserve for 5-hydroxytryptamine1A-mediated inhibition of serotonin synthesis: possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists.

TLDR
The results suggest that 5- HT1A receptor-mediated regulation of 5-HT synthesis appears to be mediated by somatodendritic autoreceptors on5-HT neurons in the midbrain raphé nuclei, and suggest that these autoreceptor possess a large receptor reserve for agonists.

Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study.

TLDR
Recombinant human (h) 5-HT1A receptor-mediated G-protein activation was characterised in membranes of transfected Chinese hamster ovary cells by use of guanosine-5'-O-(3-[35S]thio)-triphosphate ([ 35S]GTPgammaS binding) to evaluate the efficacy and potency of agonists and antagonists at recombinant human 5- HT1A receptors.

Aripiprazole, a Novel Antipsychotic, Is a High-Affinity Partial Agonist at Human Dopamine D2 Receptors

TLDR
These results, together with previous studies demonstrating partial agonist activity at serotonin 5-hydroxytryptamine (5-HT)1A receptors and antagonist activity at 5-HT2A receptors, support the identification of aripiprazole as a dopamine-serotonin system stabilizer.

Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology

TLDR
The results support the hypothesis that the unique actions of aripiprazole in humans are likely a combination of ‘functionally selective’ activation of D2 (and possibly D3)-dopamine receptors, coupled with important interactions with selected other biogenic amine receptors—particularly 5-HT receptor subtypes (5-HT1A, 5- HT2A).