Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Modulation and Absorption of Xenobiotics: The Synergistic Role of CYP450 and P-gp Activities in Cancer and Neurodegenerative Disorders

Author(s): Carmela Inglese, Maria Grazia Perrone, Francesco Berardi, Roberto Perrone and Nicola Antonio Colabufo

Volume 12, Issue 8, 2011

Page: [702 - 712] Pages: 11

DOI: 10.2174/138920011798357015

Price: $65

Abstract

P-glycoprotein (P-gp) is involved in MDR and in neurodegenerative disorders such as Parkinson disease (PD), Alzheimer disease (AD) and epilepsy. Cytochrome P450 enzymes (CYP450s) catalyze the metabolism of a wide variety of endogenous and exogenous compounds including xenobiotics, drugs, environmental toxins, steroids, and fatty acids. P-gp substrates, inhibitors and inducers should be designed and developed studying interacting mechanism with both P-gp an CYP450 enzymes before they could be employed in MDR and/or in neurodegenerative disorders. Here, the ex vivo rat everted gut sac assay has been proposed as an immediate approach to simultaneously study metabolism and transport of drugs. Elacridar, verapamil and cyclosporine A (CsA), P-gp inhibitor, substrate and modulator respectively, have been tested to validate this ex vivo approach. The new model have been used yet to develop our ligands MC18, MC266 and MC80, both as potential drugs for MDR and radiotracers for diagnosis of neurodegenerative disorders. Herein, a comparative evaluation of transport and metabolic results, by using in vitro, ex vivo and in vivo assays, is reported.

Keywords: CYP450, MC18, MC266, MC80, MDR, Neurodegenerative disorders, P-gp, rat everted gut sac assay, verapamil, cytosol


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy