2. Academic Validation
  3. Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior

Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior

  • J Med Chem. 2009 Jan 8;52(1):151-69. doi: 10.1021/jm800689g.
Stefania Butini 1,  Sandra Gemma,  Giuseppe Campiani,  Silvia Franceschini,  Francesco Trotta,  Marianna Borriello,  Nicoletta Ceres,  Sindu Ros,  Salvatore Sanna Coccone,  Matteo Bernetti,  Meri De Angelis,  Margherita Brindisi,  Vito Nacci,  Isabella Fiorini,  Ettore Novellino,  Alfredo Cagnotto,  Tiziana Mennini,  Karin Sandager-Nielsen,  Jesper Tobias Andreasen,  Jorgen Scheel-Kruger,  Jens D Mikkelsen,  Caterina Fattorusso
Affiliations

Affiliation

  • 1 European Research Centre for Drug Discovery and Development, University of Siena, Siena, Italy.
PMID: 19072656 DOI: 10.1021/jm800689g
Abstract

Dopamine D(3) antagonism combined with serotonin 5-HT(1A) and 5-HT(2A) receptor occupancy may represent a novel paradigm for developing innovative antipsychotics. The unique pharmacological features of 5i are a high affinity for dopamine D(3), serotonin 5-HT(1A) and 5-HT(2A) receptors, together with a low affinity for dopamine D(2) receptors (to minimize extrapyramidal side effects), serotonin 5-HT(2C) receptors (to reduce the risk of obesity under chronic treatment), and for hERG channels (to reduce incidence of torsade des pointes). Pharmacological and biochemical data, including specific c-Fos expression in mesocorticolimbic areas, confirmed an atypical antipsychotic profile of 5i in vivo, characterized by the absence of catalepsy at antipsychotic dose.

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