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
Research output: Contribution to journal › Journal article › Research › peer-review
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 |
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Journal | Journal of Medicinal Chemistry |
Volume | 52 |
Issue number | 1 |
Pages (from-to) | 151-69 |
Number of pages | 18 |
ISSN | 0022-2623 |
DOIs | |
Publication status | Published - 2009 |
Bibliographical 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
ID: 19977522