Effect of Iboga alkaloids on µ-opioid receptor-coupled G protein activation.
PloS one January 1, 2013 Tamara Antonio, Steven R Childers, Richard B Rothman et al. 36 citations
Iboga alkaloids, including ibogaine, its metabolite noribogaine, and the synthetic compound 18-methoxycoronaridine (18-MC), were tested for their ability to activate the μ-opioid receptor (MOR), a common target of opioid drugs. In rat thalamic membranes, all three compounds acted as antagonists, blocking the receptor rather than activating it, with functional Ke values ranging from 3 μM for ibogaine to 13 μM for noribogaine and 18-MC. None of the compounds stimulated MOR-related G protein activity in cells expressing human or rat MORs, and only limited partial agonist effects were seen in mouse MOR-expressing cells. The findings indicate that an opioid agonist mechanism does not explain these alkaloids' effects on opioid withdrawal, supporting a novel mechanism of action and justifying further search for alternative targets.