Abstract
The multireceptor strategy was implemented to obtain potential antipsychotics and/or antidepressants in a series of long-chain arylpiperazines bearing a tricyclic theophylline fragment. Their binding profile toward monoaminergic receptors (α1, 5-HT(1A), 5-HT(2A), 5-HT6, 5-HT7, D2, D3) was determined as well. The selected compounds 7 and 9 were tested in functional in vivo models and showed, like atypical antipsychotic drugs, presynaptic 5-HT(1A) receptor agonistic and postsynaptic 5-HT(1A), 5-HT(2A), and D2 receptor antagonistic activity.
Keywords:
Depression; Imidazo[2,1-f]purine-2,4-diones; Long-chain arylpiperazines; Schizophrenia; Serotonin.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antidepressive Agents, Tricyclic / chemical synthesis*
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Antidepressive Agents, Tricyclic / metabolism
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Antidepressive Agents, Tricyclic / pharmacology*
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Antipsychotic Agents / chemical synthesis*
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Antipsychotic Agents / metabolism
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Antipsychotic Agents / pharmacology*
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Behavior, Animal / drug effects
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Body Temperature Regulation / drug effects
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Dopamine D2 Receptor Antagonists / chemical synthesis
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Dopamine D2 Receptor Antagonists / pharmacology
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Male
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Mice
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Molecular Structure
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Motor Activity / drug effects
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Rats, Wistar
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Receptors, Dopamine / drug effects
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Receptors, Dopamine / metabolism
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Receptors, Serotonin / drug effects
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Receptors, Serotonin / metabolism
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Serotonin 5-HT1 Receptor Agonists / chemical synthesis
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Serotonin 5-HT1 Receptor Agonists / pharmacology
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Serotonin 5-HT1 Receptor Antagonists / chemical synthesis
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Serotonin 5-HT1 Receptor Antagonists / pharmacology
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Serotonin 5-HT2 Receptor Antagonists / chemical synthesis
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Serotonin 5-HT2 Receptor Antagonists / pharmacology
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Structure-Activity Relationship
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Theophylline / analogs & derivatives
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Theophylline / chemical synthesis*
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Theophylline / metabolism
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Theophylline / pharmacology*
Substances
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Antidepressive Agents, Tricyclic
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Antipsychotic Agents
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Dopamine D2 Receptor Antagonists
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Receptors, Dopamine
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Receptors, Serotonin
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Serotonin 5-HT1 Receptor Agonists
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Serotonin 5-HT1 Receptor Antagonists
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Serotonin 5-HT2 Receptor Antagonists
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Theophylline