Characterization of Noribogaine at nAChRs and Effect on Nicotine Self‐Administration in Rats
Émeline L. Maillet, Qing Chang, Nicolas Milon, Taleen Hanania, Mari D. Heghinian, Nandor Garamszegi, Deborah C. Mash
The FASEB Journal April 1, 2015 Peer reviewed DOI: 10.1096/fasebj.29.1_supplement.1019.2 via OpenAlex
Summary
Noribogaine, a drug with multiple pharmacological effects, was shown to decrease nicotine self-administration in rats by up to 64% compared to saline treatment. It was found to be as effective as varenicline, an established smoking cessation medication. The study characterized noribogaine's activity at specific neuronal nicotinic acetylcholine receptors and suggests its potential for treating nicotine dependence and other substance abuse-related disorders.
Study at a glance
| Design | within-subject design |
|---|---|
| Population | rats |
| Key finding | Noribogaine dose-dependently decreased nicotine self-administration by up to 64% and was equi-effective to varenicline. |
Abstract
Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, is being investigated for treatment of substance abuse‐related disorders. In this study, noribogaine molecular activity at neuronal nicotinic acetylcholine receptors (nAChRs) was characterized. Noribogaine inhibited α3β4, α7 nAChRs, and endogenously expressed habenula‐type α3‐(α5, β2, β4) nAChRs populations. Anti‐addictive compounds ibogaine, 18MC‐ a synthetic derivative of coronaridine, and mecamylamine were tested in parallel. Then, noribogaine was tested for use as a treatment for nicotine dependence in a nicotine self‐administration study in rats in comparison to varenicline, an approved medication for smoking cessation. After initial food pellet training, followed by 26 sessions of nicotine self‐administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg p.o.), noribogaine vehicle, varenicline or saline using a within‐subject design with a latin square test schedule. Noribogaine dose‐dependently decreased nicotine self‐administration by up to 64% of saline treated rats levels and was equi‐effective to varenicline. Noribogaine pharmacological profiling at the nAChRs receptor population and its ability to dose‐dependently attenuate drug‐taking behavior for nicotine supports future studies to assess its potential usefulness in multiple therapeutic arenas, including smoking cessation, substance abuse related disorders, and anxiety related disorders.