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

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


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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Antipsychotic Agents / pharmacology*
  • Biological Transport
  • Caco-2 Cells
  • Chromatography, Liquid
  • Humans
  • Mass Spectrometry
  • Protein Binding


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antipsychotic Agents
  • Adenosine Triphosphate