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Modifying quinolone antibiotics yields new anxiolytics

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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 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.

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Figure 1: Compound 4 modulates GABA-mediated currents in recombinant human GRCs.
Figure 2: Compound 4 is anxiolytic in rodent models of anxiety, without causing motor impairment.

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Acknowledgements

This research was supported by National Institute of Mental Health grant MH60527 (K.W.G.) and the Wellcome Trust (R.F.H.).

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Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, University of California, Irvine, 92697, California, USA

    Timothy B C Johnstone, Derk J Hogenkamp, Minhtam B Tran, Ryan F Yoshimura, Wen-Yen Li, Jeff Wang & Kelvin W Gee

  2. School of Biological and Biomedical Sciences, University of Durham, Durham, DH1 3LE, England, UK

    Leanne Coyne & Jiping Su

  3. Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, 95211, California, USA

    Robert F Halliwell

Authors
  1. Timothy B C Johnstone
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  2. Derk J Hogenkamp
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  3. Leanne Coyne
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  4. Jiping Su
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  5. Robert F Halliwell
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  6. Minhtam B Tran
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  7. Ryan F Yoshimura
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  8. Wen-Yen Li
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  9. Jeff Wang
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  10. Kelvin W Gee
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Correspondence to Kelvin W Gee.

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The authors declare no competing financial interests.

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Johnstone, T., Hogenkamp, D., Coyne, L. et al. Modifying quinolone antibiotics yields new anxiolytics. Nat Med 10, 31–32 (2004). https://doi.org/10.1038/nm967

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