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Noribogaine, also known as O-desmethylibogaine or 12-hydroxyibogamine, is the principal psychoactive metabolite of the oneirogen ibogaine. It is thought to be involved in the antiaddictive effects of ibogaine-containing plant extracts, such as Tabernanthe iboga.
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Noribogaine has been determined to act as a biased agonist of the κ-opioid receptor (KOR). It activates the G protein (GDP-GTP exchange) signaling pathway with 75% the efficacy of dynorphin A (EC50 = 9 μM), but it is only 12% as efficacious at activating the β-arrestin pathway. With an IC50 value of 1 μM, it can be regarded as an antagonist of the latter pathway.
The β-arrestin signaling pathway is hypothesized to be responsible for the anxiogenic, dysphoric, or anhedonic effects of KOR activation. Attenuation of the β-arrestin pathway by noribogaine may be the reason for the absence of these effects, while retaining analgesic and antiaddictive properties. This biased KOR activity makes it stand out from the other like ibogaine and the derivative 18-methoxycoronaridine (18-MC).
Noribogaine is a potent serotonin reuptake inhibitor, but does not affect the reuptake of dopamine. Unlike ibogaine, noribogaine does not bind to the sigma-2 receptor. Similarly to ibogaine, noribogaine acts as a weak NMDA receptor antagonist and binds to . It has greater affinity for each of the opioid receptors than does ibogaine. Noribogaine has been reported to be a low-maximal efficacy serotonin releasing agent, although findings are conflicting and other studies have found that it is inactive as a serotonin releasing agent.
Noribogaine is a hERG inhibitor and appears at least as potent as ibogaine. The inhibition of the hERG potassium channel delays the repolarization of cardiac action potentials, resulting in QT interval prolongation and, subsequently, in Heart arrhythmia and sudden cardiac arrest.
Noribogaine has been reported to be a potent psychoplastogen similarly to ibogaine.
Ibogaine and the structurally related hallucinogen harmaline are , whereas noribogaine is not or is much less so.
The elimination half-life of noribogaine is 24 to 50hours.
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