title: Modifying quinolone antibiotics yields new anxiolytics.
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.
authors.affiliation: Department of Pharmacology, College of Medicine, University of California, Irvine, California 92697, USA.
authors.forename: Timothy B C
authors.initials: TB
authors.lastname: Johnstone
authors.forename: Derk J
authors.initials: DJ
authors.lastname: Hogenkamp
authors.forename: Leanne
authors.initials: L
authors.lastname: Coyne
authors.forename: Jiping
authors.initials: J
authors.lastname: Su
authors.forename: Robert F
authors.initials: RF
authors.lastname: Halliwell
authors.forename: Minhtam B
authors.initials: MB
authors.lastname: Tran
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Yoshimura
authors.forename: Wen-Yen
authors.initials: WY
authors.lastname: Li
authors.forename: Jeff
authors.initials: J
authors.lastname: Wang
authors.forename: Kelvin W
authors.initials: KW
authors.lastname: Gee
mesh_terms: D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid