Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Modifying quinolone antibiotics yields new anxiolytics

Nature Medicine volume 10, pages 31–32 (2004)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Chebib, M. & Johnston, G.A. J. Med. Chem. 43, 1427–1447 (2000).

    Article  CAS  Google Scholar 

  2. Halliwell, R.F., Davey, P.G. & Lambert, J.J. J. Antimicrob. Chemother. 31, 457–462 (1993).

    Article  CAS  Google Scholar 

  3. Korpi, E.R., Grunder, G. & Luddens, H. Prog. Neurobiol. 67, 113–159 (2002).

    Article  CAS  Google Scholar 

  4. De Sarro, A. et al. Antimicrob. Agents Chemother. 43, 1729–1736 (1999).

    Article  CAS  Google Scholar 

  5. McKernan, R.M. et al. Nat. Neurosci. 3, 587–592 (2000).

    Article  CAS  Google Scholar 

  6. Vogel, J.R., Beer, B. & Clody, D.E. Psychopharmacologia (Berlin) 21, 1–7 (1971).

    Article  CAS  Google Scholar 

  7. Carboni, E., Wieland, S., Lan, N.C. & Gee, K.W. Psychopharmacology (Berlin) 126, 173–178 (1996).

    Article  CAS  Google Scholar 

  8. Crawley, J. & Goodwin, F.K. Pharmacol. Biochem. Behav. 13, 167–170 (1980).

    Article  CAS  Google Scholar 

  9. Wieland, S., Lan, N.C., Mirasedeghi, S. & Gee, K.W. Brain Res. 565, 263–268 (1991).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derk J Hogenkamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leanne Coyne
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiping Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert F Halliwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Minhtam B Tran
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ryan F Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wen-Yen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jeff Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kelvin W Gee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kelvin W Gee.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm967

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing