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

@article{Burris2002AripiprazoleAN,
  title={Aripiprazole, a Novel Antipsychotic, Is a High-Affinity Partial Agonist at Human Dopamine D2 Receptors},
  author={Kevin D. Burris and Thaddeus F. P. Molski and Cen Xu and Elaine Ryan and Katsura Tottori and Tetsuro Kikuchi and Frank D. Yocca and Perry B. Molinoff},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2002},
  volume={302},
  pages={381 - 389}
}
  • K. Burris, T. Molski, P. Molinoff
  • Published 1 July 2002
  • Psychology, Biology, Chemistry
  • Journal of Pharmacology and Experimental Therapeutics
Aripiprazole is the first next-generation atypical antipsychotic with a mechanism of action that differs from currently marketed typical and atypical antipsychotics. Aripiprazole displays properties of an agonist and antagonist in animal models of dopaminergic hypoactivity and hyperactivity, respectively. This study examined the interactions of aripiprazole with a single population of human D2 receptors to clarify further its pharmacologic properties. In membranes prepared from Chinese hamster… 

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References

SHOWING 1-10 OF 55 REFERENCES

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

Relationship between receptor occupancy and response at striatal dopamine autoreceptors.

The presence of a larger receptor reserve at pre-versus postsynaptic D2 DA receptors and the partial agonist character of drugs such as EMD 23,448 and the enantiomers of 3-PPP may account for their autoreceptor selectivity.

Receptor reserve for D2 dopaminergic inhibition of prolactin release in vivo and in vitro.

The full dopamine agonist R-(-)-N-n-propylnorapomorphine (NPA) completely suppressed serum prolactin (PRL) levels elevated by pretreatment with gamma-butyrolactone, consistent with the presence of a sizable receptor reserve at the D2 receptor regulating PRL release in the anterior pituitary.

Transdihydrolisuride, a partial dopamine receptor antagonist: effects on monoamine metabolism.

  • W. Kehr
  • Biology, Chemistry
    European journal of pharmacology
  • 1984

Lack of Discrimination by Agonists for D2 and D3 Dopamine Receptors

...