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.

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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

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. 2009 Jan 8;52(1):151-69. doi: 10.1021/jm800689g.

PubMed ID

19072656 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Aripiprazole	Dopamine D3 receptor	Ki (nM)	3.3	N/A	N/A	Details
Clozapine	Dopamine D3 receptor	Ki (nM)	319	N/A	N/A	Details
Haloperidol	Dopamine D3 receptor	Ki (nM)	0.9	N/A	N/A	Details
Olanzapine	Dopamine D3 receptor	Ki (nM)	39	N/A	N/A	Details