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 γ-aminobutyric acid (GABA) at the brain GABAA receptor complex (GRC). Modification of norfloxacin yields molecules such as compound 4 that potentiate GABA action with α2 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.