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Biochem Pharmacol. 2015 Apr 1;94(3):220-6. doi: 10.1016/j.bcp.2015.01.008. Epub 2015 Jan 28.

P-glycoprotein interactions of novel psychoactive substances - stimulation of ATP consumption and transport across Caco-2 monolayers.

Author information

1
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421 Homburg, Germany. Electronic address: markus.meyer@uks.eu.
2
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421 Homburg, Germany.
3
Dept of Drug Delivery, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Center for Infection Research, Saarland University, 66123 Saarbrücken, Germany.

Abstract

In contrast to drugs for therapeutic use, there are only few data available concerning interactions between P-glycoprotein (P-gp) and drugs of abuse (DOA). In this work, interactions between structurally diverse DOA and P-gp were investigated using different strategies. First, the effect on the P-gp ATPase activity was studied by monitoring of ATP consumption after addition to recombinant, human P-gp. Second, DOA showing an increased ATP consumption were further characterized regarding their transport across filter grown Caco-2- monolayers. Analyses were performed by luminescence and liquid chromatography-mass spectrometry, respectively. Among the nine DOA initially screened, benzedrone, diclofensine, glaucine, JWH-200, MDBC, WIN-55,212-2 showed an increase of ATP consumption in the ATPase stimulation assay. In Caco-2 transport studies, Glaucine, JWH-200, mitragynine, WIN-55,212-2 could moreover be identified as non-transported substrates, but inhibitors of P-gp activity. Thus, drug-drug or drug-food interactions should be very likely for these compounds.

KEYWORDS:

Drugs of abuse; Inhibitor; Novel psychoactive substances; Substrate; p-Glycoprotein

PMID:
25637762
DOI:
10.1016/j.bcp.2015.01.008
[Indexed for MEDLINE]

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