Abstract
Patients taking fluoroquinolone antibiotics such as norfloxacin exhibit a low incidence of convulsions and anxiety. These side effects probably result from antagonism of the neurotransmitter gamma-aminobutyric acid (GABA) at the brain GABA(A) receptor complex (GRC). Modification of norfloxacin yields molecules such as compound 4 that potentiate GABA action with alpha(2) subunit selectivity. Compound 4 is anxiolytic but does not cause sedation, and may represent a new class of ligands that have anxiolytic activity without sedative liability.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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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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Anti-Infective Agents / chemistry
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Anti-Infective Agents / metabolism
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Anti-Infective Agents / pharmacology*
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Fluoroquinolones / chemistry
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Fluoroquinolones / metabolism
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Fluoroquinolones / pharmacology*
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Humans
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Protein Binding
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Receptors, GABA-A / metabolism
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Recombinant Proteins / metabolism
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gamma-Aminobutyric Acid / metabolism
Substances
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Anti-Anxiety Agents
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Anti-Infective Agents
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Fluoroquinolones
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Receptors, GABA-A
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Recombinant Proteins
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gamma-Aminobutyric Acid