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Phenylpiperidine selective serotonin reuptake inhibitors interfere with multidrug efflux pump activity in
Glenn W Kaatz1, Varsha V Moudgal, Susan M Seo
1Division of Infectious Diseases, The John D. Dingell Department of Veterans Affairs Medical Center and the Department of Internal Medicine, Wayne State University School of Medicine, B4333, 4646 John R, Detroit, MI 48201, USA. gkaatz@juno.com
Abstract:
Structural variants of phenylpiperidine selective serotonin reuptake inhibitors (P-SSRIs) inhibited the function of two unique Staphylococcus aureus multidrug efflux pumps. The most active compound was the paroxetine isomer NNC 20-7052, which had an IC(50) for ethidium, acriflavine, and pyronin Y efflux of 9, 53, and 18% of its MIC, respectively, against the NorA pump. The unbalanced effect of NNC 20-7052 on the efflux of different substrates suggests the possibility that P-SSRIs function by a physical interaction with NorA. Under the conditions employed pump inhibition partially extended to the resistance-nodulation-division (RND) pump AcrAB-TolC, but not to the Pseudomonas aeruginosa RND pumps MexAB-OprM or MexCD-OprJ.