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Modulation of Glutamate and Glycine Transporters by Niflumic, Flufenamic and Mefenamic Acids

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Abstract

Three fenamates—niflumic, flufenamic and mefenamic acids—were tested for effects on substrate-induced currents of glutamate and glycine transporters (EAAT1, EAAT2, GLYT1b and GLYT2a) expressed in Xenopus laevis oocytes. All fenamates inhibited EAAT1 currents; 100 μM flufenamic acid produced the most inhibition, decreasing the I max by 53 ± 4% (P < 0.001). EAAT2 currents were less sensitive, but 100 μM flufenamic acid inhibited the I max by 34 ± 5% (P = 0.006). All fenamates inhibited GLYT1b currents; 100 μM flufenamic acid produced the most inhibition, decreasing the I max by 61 ± 1% (P < 0.001). At 100 μM, effects on the GLYT2a I max were mixed: 13 ± 2% inhibition by flufenamic acid (P = 0.002), 30 ± 6% enhancement by niflumic acid (P = 0.002), and no effect by mefenamic acid. Minor effects on substrate affinity suggested non-competitive mechanisms. These data could contribute to the development of selective transport modulators.

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Acknowledgments

Professor Graham Johnston is gratefully acknowledged for giving Robert Vandenberg the opportunity to establish the transporter biology group in the Discipline of Pharmacology at the University of Sydney. Professor Johnston’s mentorship and guidance, as Associate Supervisor for Suzanne Habjan during her PhD candidature, are highly appreciated. We thank staff and students who contributed to maintenance of the Xenopus laevis colony and isolation of oocytes, and the Australian Government National Health and Medical Research Council and the University of Sydney for supporting this work.

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  1. Discipline of Pharmacology, Bosch Institute, University of Sydney, Blackburn Building (D06), Sydney, NSW, 2006, Australia

    Suzanne Habjan & Robert J. Vandenberg

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  1. Suzanne Habjan
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  2. Robert J. Vandenberg
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Correspondence to Robert J. Vandenberg.

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Habjan, S., Vandenberg, R.J. Modulation of Glutamate and Glycine Transporters by Niflumic, Flufenamic and Mefenamic Acids. Neurochem Res 34, 1738–1747 (2009). https://doi.org/10.1007/s11064-009-9983-y

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