Drug intelligence / Profile preview

noribogaine

Development stage
Phase 1
Lead developer
DemeRx NB
Modality
Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Oral, Transdermal, Systemic (unspecified)
01

Overview

Noribogaine is the principal psychoactive metabolite of ibogaine, formed via O-demethylation. It is a naturally occurring alkaloid found in plants of the Apocynaceae family, notably Tabernanthe iboga. Noribogaine exhibits complex pharmacology and is thought to be primarily responsible for many of the antiaddictive effects attributed to ibogaine-containing preparations. Mechanistically, it acts as a potent serotonin reuptake inhibitor and has higher affinity than its parent compound for both κ-opioid (KOR) and μ-opioid receptors, where it functions as a biased agonist at KOR (favoring G protein signaling over β-arrestin recruitment) and likely as a partial agonist or antagonist at μ-opioid receptors. Noribogaine also acts as a weak NMDA receptor antagonist and inhibits hERG potassium channels, which can lead to QT prolongation and cardiac arrhythmias. Its long half-life in humans (28–49 hours) may contribute to sustained effects on opioid withdrawal symptoms by modulating serotonergic and opioid systems[1][2][4][7].

Other names
O-desmethylibogaine12-hydroxyibogamine12-OH-ibogamine
02

Targets

NMDAR (Glutamate receptor ionotropic, NMDA)SERT (Sodium-dependent serotonin transporter)KCNH2 (Voltage-gated potassium channel subfamily H member 2)KOR (Kappa opioid receptor)MOR (Mu opioid receptor)

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