Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies

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

Standard

Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics : Synthesis, Biological Characterization, and Behavioral Studies. / Brindisi, Margherita; Butini, Stefania; Franceschini, Silvia; Brogi, Simone; Trotta, Francesco; Ros, Sindu; Cagnotto, Alfredo; Salmona, Mario; Casagni, Alice; Andreassi, Marco; Saponara, Simona; Gorelli, Beatrice; Weikop, Pia; Mikkelsen, Jens D.; Scheel-Kruger, Jorgen; Sandager-Nielsen, Karin; Novellino, Ettore; Campiani, Giuseppe; Gemma, Sandra.

In: Journal of Medicinal Chemistry, Vol. 57, No. 22, 26.11.2014, p. 9578-9597.

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

Harvard

Brindisi, M, Butini, S, Franceschini, S, Brogi, S, Trotta, F, Ros, S, Cagnotto, A, Salmona, M, Casagni, A, Andreassi, M, Saponara, S, Gorelli, B, Weikop, P, Mikkelsen, JD, Scheel-Kruger, J, Sandager-Nielsen, K, Novellino, E, Campiani, G & Gemma, S 2014, 'Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies', Journal of Medicinal Chemistry, vol. 57, no. 22, pp. 9578-9597. https://doi.org/10.1021/jm501119j

APA

Brindisi, M., Butini, S., Franceschini, S., Brogi, S., Trotta, F., Ros, S., Cagnotto, A., Salmona, M., Casagni, A., Andreassi, M., Saponara, S., Gorelli, B., Weikop, P., Mikkelsen, J. D., Scheel-Kruger, J., Sandager-Nielsen, K., Novellino, E., Campiani, G., & Gemma, S. (2014). Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies. Journal of Medicinal Chemistry, 57(22), 9578-9597. https://doi.org/10.1021/jm501119j

Vancouver

Brindisi M, Butini S, Franceschini S, Brogi S, Trotta F, Ros S et al. Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies. Journal of Medicinal Chemistry. 2014 Nov 26;57(22):9578-9597. https://doi.org/10.1021/jm501119j

Author

Brindisi, Margherita ; Butini, Stefania ; Franceschini, Silvia ; Brogi, Simone ; Trotta, Francesco ; Ros, Sindu ; Cagnotto, Alfredo ; Salmona, Mario ; Casagni, Alice ; Andreassi, Marco ; Saponara, Simona ; Gorelli, Beatrice ; Weikop, Pia ; Mikkelsen, Jens D. ; Scheel-Kruger, Jorgen ; Sandager-Nielsen, Karin ; Novellino, Ettore ; Campiani, Giuseppe ; Gemma, Sandra. / Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics : Synthesis, Biological Characterization, and Behavioral Studies. In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 22. pp. 9578-9597.

Bibtex

@article{7135d03324a4494aa80fe8d083bbb39a,
title = "Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies",
abstract = "Combination of dopamine D3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structure-activity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.",
keywords = "Amides, Animals, Antipsychotic Agents, Behavior, Animal, Dizocilpine Maleate, Dopamine Antagonists, Drug Evaluation, Preclinical, Female, Kinetics, Ligands, Male, Mice, Prefrontal Cortex, Protein Binding, Rats, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT1A, Receptor, Serotonin, 5-HT2A, Receptors, Dopamine D3, Schizophrenia, Serotonin Receptor Agonists, Structure-Activity Relationship",
author = "Margherita Brindisi and Stefania Butini and Silvia Franceschini and Simone Brogi and Francesco Trotta and Sindu Ros and Alfredo Cagnotto and Mario Salmona and Alice Casagni and Marco Andreassi and Simona Saponara and Beatrice Gorelli and Pia Weikop and Mikkelsen, {Jens D.} and Jorgen Scheel-Kruger and Karin Sandager-Nielsen and Ettore Novellino and Giuseppe Campiani and Sandra Gemma",
year = "2014",
month = nov,
day = "26",
doi = "10.1021/jm501119j",
language = "English",
volume = "57",
pages = "9578--9597",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "22",

}

RIS

TY - JOUR

T1 - Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics

T2 - Synthesis, Biological Characterization, and Behavioral Studies

AU - Brindisi, Margherita

AU - Butini, Stefania

AU - Franceschini, Silvia

AU - Brogi, Simone

AU - Trotta, Francesco

AU - Ros, Sindu

AU - Cagnotto, Alfredo

AU - Salmona, Mario

AU - Casagni, Alice

AU - Andreassi, Marco

AU - Saponara, Simona

AU - Gorelli, Beatrice

AU - Weikop, Pia

AU - Mikkelsen, Jens D.

AU - Scheel-Kruger, Jorgen

AU - Sandager-Nielsen, Karin

AU - Novellino, Ettore

AU - Campiani, Giuseppe

AU - Gemma, Sandra

PY - 2014/11/26

Y1 - 2014/11/26

N2 - Combination of dopamine D3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structure-activity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.

AB - Combination of dopamine D3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structure-activity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.

KW - Amides

KW - Animals

KW - Antipsychotic Agents

KW - Behavior, Animal

KW - Dizocilpine Maleate

KW - Dopamine Antagonists

KW - Drug Evaluation, Preclinical

KW - Female

KW - Kinetics

KW - Ligands

KW - Male

KW - Mice

KW - Prefrontal Cortex

KW - Protein Binding

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptor, Serotonin, 5-HT1A

KW - Receptor, Serotonin, 5-HT2A

KW - Receptors, Dopamine D3

KW - Schizophrenia

KW - Serotonin Receptor Agonists

KW - Structure-Activity Relationship

U2 - 10.1021/jm501119j

DO - 10.1021/jm501119j

M3 - Journal article

C2 - 25343529

VL - 57

SP - 9578

EP - 9597

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 22

ER -

ID: 137315302