Kratom (Mitragyna speciosa)
P-glycoprotein interactions of novel psychoactive substances – Stimulation of ATP consumption and transport across Caco-2 monolayers CSV JSON

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

1 . Mitragynine Inhibition (id=NPDI-E56YVg)

In Vitro Transporter Inhibition Experiment

Inhibition was detected.  Cutoff used — Unspecified

Rhodamine 123

Mitragynine

  • P-gp (ABCB1)

Cell system Caco-2 cells

p<0.05 Values determined from Fig. 5

Results

Results for Mitragynine+R123 were statistically significant (p<0.05) vs R123 alone. Values from Fig. 5

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Preincubated with KRB for 60 min

Cell Culture Conditions

60,000 cells/well

Transwell

21-23

54–72

Viability and Function

>300 V cm2

Epithelial Voltohmmeter (EVOM2) coupled with a STX2 ‘chopstick’ electrode (World Precision Instruments)

Assay Conditions

180 m

37 deg C

7.4

5 µM

5 µM

Department of Forensic Medicine, Johannes Gutenberg University (Mainz, Germany), where it was isolated from Kratom leaves obtained from head&nature

Control Experiment Information