Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine d3 and serotonin 5-HT 1A and 5-HT2A receptors: Design, synthesis, and effects on behavior

Stefania Butini, 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-KrugerJens D. Mikkelsen, Caterina Fattorusso

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Dopamine D3 antagonism combined with serotonin 5-HT1A and 5-HT2A receptor occupancy may represent a novel paradigm for developing innovative antipsychotics. The unique pharmacological features of 5i are a high affinity for dopamine D3, serotonin 5-HT1A and 5-HT2A receptors, together with a low affinity for dopamine D 2 receptors (to minimize extrapyramidal side effects), serotonin 5-HT2C 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.copy; 2009 American Chemical Society.

Original languageEnglish
Pages (from-to)151-169
Number of pages19
JournalJournal of Medicinal Chemistry
Volume52
Issue number1
DOIs
Publication statusPublished - Jan 8 2009

Fingerprint

Receptor, Serotonin, 5-HT2A
Antipsychotic Agents
Dopamine
Serotonin
Pharmacology
Receptor, Serotonin, 5-HT2C
Catalepsy
Obesity
Incidence

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine d3 and serotonin 5-HT 1A and 5-HT2A receptors : Design, synthesis, and effects on behavior. / Butini, Stefania; Gemma, Sandra; Campiani, Giuseppe; Franceschini, Silvia; Trotta, Francesco; Borriello, Marianna; Ceres, Nicoletta; Ros, Sindu; Coccone, Salvatore Sanna; Bernetti, Matteo; De Angelis, Meri; Brindisi, Margherita; Nacci, Vito; Fiorini, Isabella; Novellino, Ettore; Cagnotto, Alfredo; Mennini, Tiziana; Sandager-Nielsen, Karin; Andreasen, Jesper Tobias; Scheel-Kruger, Jorgen; Mikkelsen, Jens D.; Fattorusso, Caterina.

In: Journal of Medicinal Chemistry, Vol. 52, No. 1, 08.01.2009, p. 151-169.

Research output: Contribution to journalArticle

Butini, S, Gemma, S, Campiani, G, Franceschini, S, Trotta, F, Borriello, M, Ceres, N, Ros, S, Coccone, SS, Bernetti, M, De Angelis, M, Brindisi, M, Nacci, V, Fiorini, I, Novellino, E, Cagnotto, A, Mennini, T, Sandager-Nielsen, K, Andreasen, JT, Scheel-Kruger, J, Mikkelsen, JD & Fattorusso, C 2009, 'Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine d3 and serotonin 5-HT 1A and 5-HT2A receptors: Design, synthesis, and effects on behavior', Journal of Medicinal Chemistry, vol. 52, no. 1, pp. 151-169. https://doi.org/10.1021/jm800689g
Butini, Stefania ; Gemma, Sandra ; Campiani, Giuseppe ; Franceschini, Silvia ; Trotta, Francesco ; Borriello, Marianna ; Ceres, Nicoletta ; Ros, Sindu ; Coccone, Salvatore Sanna ; Bernetti, Matteo ; De Angelis, Meri ; Brindisi, Margherita ; Nacci, Vito ; Fiorini, Isabella ; Novellino, Ettore ; Cagnotto, Alfredo ; Mennini, Tiziana ; Sandager-Nielsen, Karin ; Andreasen, Jesper Tobias ; Scheel-Kruger, Jorgen ; Mikkelsen, Jens D. ; Fattorusso, Caterina. / Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine d3 and serotonin 5-HT 1A and 5-HT2A receptors : Design, synthesis, and effects on behavior. In: Journal of Medicinal Chemistry. 2009 ; Vol. 52, No. 1. pp. 151-169.
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