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Modifying quinolone antibiotics yields new anxiolytics

Nature Medicine volume 10, pages 3132 (2004) | Download Citation

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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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References

  1. 1.

    & J. Med. Chem. 43, 1427–1447 (2000).

  2. 2.

    , & J. Antimicrob. Chemother. 31, 457–462 (1993).

  3. 3.

    , & Prog. Neurobiol. 67, 113–159 (2002).

  4. 4.

    et al. Antimicrob. Agents Chemother. 43, 1729–1736 (1999).

  5. 5.

    et al. Nat. Neurosci. 3, 587–592 (2000).

  6. 6.

    , & Psychopharmacologia (Berlin) 21, 1–7 (1971).

  7. 7.

    , , & Psychopharmacology (Berlin) 126, 173–178 (1996).

  8. 8.

    & Pharmacol. Biochem. Behav. 13, 167–170 (1980).

  9. 9.

    , , & Brain Res. 565, 263–268 (1991).

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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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Affiliations

  1. Department of Pharmacology, College of Medicine, University of California, Irvine, California 92697, 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, England DH1 3LE, UK.

    • Leanne Coyne
    •  & Jiping Su
  3. Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California 95211, USA.

    • Robert F Halliwell

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The authors declare no competing financial interests.

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Correspondence to Kelvin W Gee.

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DOI

https://doi.org/10.1038/nm967