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
; 52(1): 151-69, 2009 Jan 08.
Article
in En
| MEDLINE
| ID: mdl-19072656
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antipsychotic Agents
/
Behavior, Animal
/
Drug Design
/
Receptor, Serotonin, 5-HT1A
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Receptor, Serotonin, 5-HT2A
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Receptors, Dopamine D3
Limits:
Animals
/
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2009
Document type:
Article
Affiliation country:
Italy