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

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-Kruger; Jens D Mikkelsen; Caterina Fattorusso

doi:10.1021/jm800689g

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

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

Department of Neuroscience

73 Citations (Scopus)

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.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	52
Issue number	1
Pages (from-to)	151-69
Number of pages	18
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm800689g
Publication status	Published - 2009

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/jm800689g

Cite this

Butini, S., Gemma, S., Campiani, G., Franceschini, S., Trotta, F., Borriello, M., Ceres, N., Ros, S., Coccone, S. S., Bernetti, M., De Angelis, M., Brindisi, M., Nacci, V., Fiorini, I., Novellino, E., Cagnotto, A., Mennini, T., Sandager-Nielsen, K., Andreasen, J. T., ... Fattorusso, C. (2009). 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. Journal of Medicinal Chemistry, 52(1), 151-69. https://doi.org/10.1021/jm800689g

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. / Butini, Stefania; Gemma, Sandra; Campiani, Giuseppe et al.

In: Journal of Medicinal Chemistry, Vol. 52, No. 1, 2009, p. 151-69.

Research output: Contribution to journal › Journal article › Research › peer-review

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-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior', Journal of Medicinal Chemistry, vol. 52, no. 1, pp. 151-69. https://doi.org/10.1021/jm800689g

@article{3229ce1068a411df928f000ea68e967b,

title = "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",

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.",

author = "Stefania Butini and Sandra Gemma and Giuseppe Campiani and Silvia Franceschini and Francesco Trotta and Marianna Borriello and Nicoletta Ceres and Sindu Ros and Coccone, {Salvatore Sanna} and Matteo Bernetti and {De Angelis}, Meri and Margherita Brindisi and Vito Nacci and Isabella Fiorini and Ettore Novellino and Alfredo Cagnotto and Tiziana Mennini and Karin Sandager-Nielsen and Andreasen, {Jesper Tobias} and Jorgen Scheel-Kruger and Mikkelsen, {Jens D} and Caterina Fattorusso",

note = "Keywords: Animals; Antipsychotic Agents; Behavior, Animal; Binding Sites; Drug Design; Drug Evaluation, Preclinical; Humans; Ligands; Mice; Models, Molecular; Molecular Structure; Protein Binding; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D3; Structure-Activity Relationship",

year = "2009",

doi = "10.1021/jm800689g",

language = "English",

volume = "52",

pages = "151--69",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "1",

}

TY - JOUR

T1 - 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

AU - Butini, Stefania

AU - Gemma, Sandra

AU - Campiani, Giuseppe

AU - Franceschini, Silvia

AU - Trotta, Francesco

AU - Borriello, Marianna

AU - Ceres, Nicoletta

AU - Ros, Sindu

AU - Coccone, Salvatore Sanna

AU - Bernetti, Matteo

AU - De Angelis, Meri

AU - Brindisi, Margherita

AU - Nacci, Vito

AU - Fiorini, Isabella

AU - Novellino, Ettore

AU - Cagnotto, Alfredo

AU - Mennini, Tiziana

AU - Sandager-Nielsen, Karin

AU - Andreasen, Jesper Tobias

AU - Scheel-Kruger, Jorgen

AU - Mikkelsen, Jens D

AU - Fattorusso, Caterina

N1 - Keywords: Animals; Antipsychotic Agents; Behavior, Animal; Binding Sites; Drug Design; Drug Evaluation, Preclinical; Humans; Ligands; Mice; Models, Molecular; Molecular Structure; Protein Binding; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D3; Structure-Activity Relationship

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1021/jm800689g

DO - 10.1021/jm800689g

M3 - Journal article

C2 - 19072656

SN - 0022-2623

VL - 52

SP - 151

EP - 169

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 1

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this