Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2).
Nicolas Tournier, Lucie Chevillard, Bruno Mégarbane, Stéphane Pirnay, Jean-Michel Scherrmann, Xavier Declèves
The International Journal of Neuropsychopharmacology August 1, 2010 DOI: 10.1017/S1461145709990848 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells |
| Interventions | buprenorphine norbuprenorphine methadone ibogaine cocaine cocaethylene amphetamine N-methyl-3 4-methylenedioxyamphetamine 3 nicotine ketamine Delta9-tetrahydrocannabinol naloxone morphine |
| Topics | Cannabis Ibogaine |
| Keywords | Drug transport Drug movement Drug distribution Drug efflux Active transport Body distribution Drug permeability Addiction treatment Addiction drugs Substance abuse treatment Methadone Norbuprenorphine Drug-protein interaction Protein inhibition P-glycoprotein Bcrp Transporter proteins Efflux pumps Pharmacokinetics Drug disposition Drug metabolism Drug absorption Drug elimination Drug pharmacology |
| Citations | 122 |
| Key points | Norbuprenorphine, buprenorphine, methadone, ibogaine, and THC inhibit P-gp, while buprenorphine, norbuprenorphine, ibogaine, and THC inhibit BCRP, with only norbuprenorphine and methadone being transported by P-gp. |
Abstract
Drug interaction with P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may influence its tissue disposition including blood-brain barrier transport and result in potent drug-drug interactions. The limited data obtained using in-vitro models indicate that methadone, buprenorphine, and cannabinoids may interact with human P-gp; but almost nothing is known about drugs of abuse and BCRP. We used in vitro P-gp and BCRP inhibition flow cytometric assays with hMDR1- and hBCRP-transfected HEK293 cells to test 14 compounds or metabolites frequently involved in addiction, including buprenorphine, norbuprenorphine, methadone, ibogaine, cocaine, cocaethylene, amphetamine, N-methyl-3,4-methylenedioxyamphetamine, 3,4-methylenedioxyamphetamine, nicotine, ketamine, Delta9-tetrahydrocannabinol (THC), naloxone, and morphine. Drugs that in vitro inhibited P-gp or BCRP were tested in hMDR1- and hBCRP-MDCKII bidirectional transport studies. Human P-gp was significantly inhibited in a concentration-dependent manner by norbuprenorphine>buprenorphine>methadone>ibogaine and THC. Similarly, BCRP was inhibited by buprenorphine>norbuprenorphine>ibogaine and THC. None of the other tested compounds inhibited either transporter, even at high concentration (100 microm). Norbuprenorphine (transport efflux ratio approoximately 11) and methadone (transport efflux ratio approoximately 1.9) transport was P-gp-mediated; however, with no significant stereo-selectivity regarding methadone enantiomers. BCRP did not transport any of the tested compounds. However, the clinical significance of the interaction of norbuprenorphine with P-gp remains to be evaluated.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 5
- The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020). Psychopharmacology June 1, 2022
- Main targets of ibogaine and noribogaine associated with its putative anti-addictive effects: A mechanistic overview. Journal of Psychopharmacology December 1, 2023
- Drug Transporters ABCB1 (P-gp) and OATP, but not Drug-Metabolizing Enzyme CYP3A4, Affect the Pharmacokinetics of the Psychoactive Alkaloid Ibogaine and its Metabolites. Frontiers in Pharmacology 2022
- ATP-binding cassette transporter polymorphisms and the pharmacokinetics of oral esketamine Pharmacogenomics December 12, 2025
- Review of delta‐8‐tetrahydrocannabinol (Δ8‐THC): Comparative pharmacology with Δ9‐THC British Journal of Pharmacology August 1, 2022