Modifying quinolone antibiotics yields new anxiolytics.
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.
Johnstone
Timothy B C
TB
Department of Pharmacology, College of Medicine, University of California, Irvine, California 92697, USA.
Hogenkamp
Derk J
DJ
Coyne
Leanne
L
Su
Jiping
J
Halliwell
Robert F
RF
Tran
Minhtam B
MB
Yoshimura
Ryan F
RF
Li
Wen-Yen
WY
Wang
Jeff
J
Gee
Kelvin W
KW
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
D014151:Anti-Anxiety Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid