Abstract
The mitochondrial translocator protein (TSPO) mediates the synthesis of neurosteroids in the CNS, which have been demonstrated to enhance the neurotransmitter GABA response, exhibiting related behavioural properties. Selective TSPO ligands are able to stimulate steroidogenesis with great efficacy, thus representing potential anxiolytic agents. This review describes the development of a class of high affinity ligands to TSPO, N,N-dialkylindol-3-ylglyoxylamides (IGA), from the initial stages of design to the pharmacological characterization of selected compounds for their anxiolytic activity. Affinity data and SARs of the new class of ligands are discussed; the potential applications of compounds characterized by the indolylglyoxylyl scaffold in diagnostic imaging are also pointed out.
MeSH terms
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Amides / chemistry*
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Amides / metabolism
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Amides / pharmacology
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Animals
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Anti-Anxiety Agents / chemistry*
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Anti-Anxiety Agents / metabolism
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Anti-Anxiety Agents / pharmacology
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Binding Sites
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Brain / drug effects*
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Brain / metabolism
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GABA-A Receptor Agonists / chemistry
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GABA-A Receptor Agonists / metabolism
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GABA-A Receptor Agonists / pharmacology
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GABA-A Receptor Antagonists / chemistry
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GABA-A Receptor Antagonists / metabolism
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GABA-A Receptor Antagonists / pharmacology
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Glyoxylates / chemistry*
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Glyoxylates / metabolism
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Glyoxylates / pharmacology
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Humans
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Indoles / chemistry*
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Indoles / metabolism
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Indoles / pharmacology
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Ligands
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Neurotransmitter Agents / metabolism
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Protein Binding
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Protein Subunits / agonists
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Protein Subunits / antagonists & inhibitors
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Protein Subunits / metabolism
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Receptors, GABA / metabolism*
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Receptors, GABA-A / metabolism*
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Structure-Activity Relationship
Substances
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Amides
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Anti-Anxiety Agents
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GABA-A Receptor Agonists
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GABA-A Receptor Antagonists
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Glyoxylates
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Indoles
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Ligands
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Neurotransmitter Agents
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Protein Subunits
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Receptors, GABA
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Receptors, GABA-A
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TSPO protein, human