Abstract
Serotonin antagonist reuptake inhibitor (SARI) drugs that block both 5-HT(2) receptors and the serotonin transporters have been developed. The human 5-HT(2A/2C) receptor has been implicated in several neurological conditions, and potent selective 5-HT(2A/2C) ligands may have therapeutic potential for treatment of CNS diseases such as depression. An imidazole moiety usually provides good pharmacokinetic properties as a drug substance, and thus considerable efforts have been devoted to develop imidazole derivatives into drug candidates. The imidazole series of compounds was evaluated against 5-HT(2A/2C) and serotonin reuptake inhibition. A few of the compounds in the series showed promising IC(50) values and antidepressant-like effect in in vivo forced swimming test (FST). On the basis of these results, further lead optimization studies resulted in identifying promising compounds potentially for therapeutic use.
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 / chemical synthesis*
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Antidepressive Agents / pharmacokinetics
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Antidepressive Agents / pharmacology
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Binding, Competitive
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CHO Cells
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Cricetinae
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Cricetulus
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Drug Design
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / pharmacokinetics
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Imidazoles / pharmacology
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Male
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Mice
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Motor Activity / drug effects
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Piperazines / chemical synthesis*
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Piperazines / pharmacokinetics
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Piperazines / pharmacology
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptor, Serotonin, 5-HT2A / metabolism*
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Selective Serotonin Reuptake Inhibitors / chemical synthesis*
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Selective Serotonin Reuptake Inhibitors / pharmacokinetics
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Selective Serotonin Reuptake Inhibitors / pharmacology
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Serotonin 5-HT2 Receptor Antagonists / chemical synthesis*
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Serotonin 5-HT2 Receptor Antagonists / pharmacokinetics
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Serotonin 5-HT2 Receptor Antagonists / pharmacology
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Serotonin Plasma Membrane Transport Proteins / metabolism*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antidepressive Agents
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Imidazoles
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Piperazines
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Receptor, Serotonin, 5-HT2A
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Serotonin 5-HT2 Receptor Antagonists
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Serotonin Plasma Membrane Transport Proteins
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Serotonin Uptake Inhibitors