[{"id":53,"uid":"NPDI-Yknaag","name":"P-glycoprotein interactions of novel psychoactive substances – Stimulation of ATP consumption and transport across Caco-2 monolayers","napdiIdentifier":null,"overallSummary":"
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
\r\nUnspecified
","croIdentifier":null,"comment":"Positive control - verapamil (5 µM) ER of 7.4
","experimentalConditionsComment":null,"resultsComment":"Values from Fig 5","internalComment":null,"objectCompoundId":95,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":53,"experimentTypeId":7,"testSystemId":35,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":7,"name":"In Vitro Transporter Kinetics","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005003"},"objectCompound":{"id":95,"name":"rhodamine 123","unii":null,"inChIKey":"MYFATKRONKHHQL-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":null,"objectMetaboliteCompound":null,"enzymes":[],"transporters":[{"id":11,"name":"P-gp (ABCB1)","conceptId":null,"experiment_transporter_xref":{"experiment":233,"transporte":11}}],"quantifiedMetabolites":[]},{"id":232,"uid":"NPDI-E56YVg","name":"Mitragynine Inhibition","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"Unspecified
","croIdentifier":null,"comment":"p<0.05 Values determined from Fig. 5
","experimentalConditionsComment":"Preincubated with KRB for 60 min