Abstract
The synthesis, structure-affinity relationship and activity of benzyloxyphenethyl piperazine derivatives combining NK(1) antagonism and serotonin reuptake inhibition is described. Compound 7u was shown to be active in animal models of 5-HT reuptake inhibition and central NK(1) receptor blockade, and was demonstrated to be orally active in an integrated model sensitive to both mechanisms. This class of compounds potentially represents a new generation of antidepressants.
MeSH terms
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Alcohols / chemical synthesis
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Alcohols / pharmacology
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Antidepressive Agents, Second-Generation / chemical synthesis*
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Antidepressive Agents, Second-Generation / pharmacology*
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Carrier Proteins / drug effects
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Central Nervous System / drug effects
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Central Nervous System / metabolism
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Drug Evaluation, Preclinical
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Humans
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Membrane Glycoproteins / drug effects
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Membrane Transport Proteins*
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Nerve Tissue Proteins*
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Neurokinin-1 Receptor Antagonists*
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Piperazines / chemical synthesis*
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Piperazines / pharmacology*
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Selective Serotonin Reuptake Inhibitors / chemical synthesis*
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Selective Serotonin Reuptake Inhibitors / pharmacology*
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Serotonin Plasma Membrane Transport Proteins
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Structure-Activity Relationship
Substances
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Alcohols
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Antidepressive Agents, Second-Generation
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Carrier Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Neurokinin-1 Receptor Antagonists
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Piperazines
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SLC6A4 protein, human
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Serotonin Plasma Membrane Transport Proteins
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Serotonin Uptake Inhibitors
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benzyloxyphenethyl piperazine