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Effect of the novel antipsychotic drug perospirone on P-glycoprotein function and expression in Caco-2 cells

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

Perospirone (PER) is a novel atypical antipsychotic drug for the treatment of schizophrenia and other psychotic disorders. The multidrug resistance transporter, P-glycoprotein (Pgp), is involved in the efflux transport of several antipsychotics across the blood-brain barrier (BBB).The aim of the present study was to evaluate the modulating effect of PER on both Pgp activity and expression in Caco-2 cell monolayers.

Methods

The effects of PER were analyzed by means of rhodamine 123 (Rhd 123) assays, and those of Pgp expression were analyzed by flow cytometry and reverse transcriptase-PCR.

Results

Perospirone at concentrations of 0.01–30 μM, which were found to be non-cytotoxic towards the Caco-2 cells, was observed to inhibit Pgp-mediated efflux transport of Rhd 123 in the cells as well as to down-regulate the cellular Pgp protein and MDR1 mRNA levels in a concentration-dependent manner. In the rhodamine accumulation assays, 30 μM PER produced a 429% increase of the cellular Rhd 123 concentration, which exceeded the inhibitory effect of the well-known Pgp inhibitor verapamil.

Conclusion

Our findings provide experimental evidence that PER is an inhibitor of Pgp which interferes directly and indirectly with the function of Pgp.

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Acknowledgments

We thank Dr Di-Lan Qin for excellent technical assistance. None of the authors have conflicting interests that interfere with the integrity of the content of the article.

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Authors and Affiliations

  1. The Clinical Pharmacy & Pharmacology Institute, XiangYa Second Hospital, Central South University, Changsha, 410011, China

    Yan-Gang Zhou & Huan-De Li

  2. Clinical Pharmaceutical Research Institute, Hunan Provincial Tumor Hospital, Changsha, China

    Kun-Yan Li

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  1. Yan-Gang Zhou
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Correspondence to Huan-De Li.

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Zhou, YG., Li, KY. & Li, HD. Effect of the novel antipsychotic drug perospirone on P-glycoprotein function and expression in Caco-2 cells. Eur J Clin Pharmacol 64, 697–703 (2008). https://doi.org/10.1007/s00228-008-0487-5

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  • DOI: https://doi.org/10.1007/s00228-008-0487-5

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