Noribogaine

Noribogaine

Legal status
Legal status	AU: S4 (Prescription only) US: Unscheduled (but still a Schedule I analogue due to being a main metabolite of C-I ibogaine)
Identifiers
IUPAC name 12-Hydroxyibogamine
CAS Number	481-88-9 N
PubChem CID	3083548
ChemSpider	2340735 Y
Chemical and physical data
Formula	C19H24N2O
Molar mass	296.407 g/mol
3D model (Jmol)	Interactive image
SMILES CC[C@H]1C[C@@H]2C[C@@H]3[C@H]1N(C2)CCC4=C3NC5=C4C=C(C=C5)O
InChI InChI=1S/C19H24N2O/c1-2-12-7-11-8-16-18-14(5-6-21(10-11)19(12)16)15-9-13(22)3-4-17(15)20-18/h3-4,9,11-12,16,19-20,22H,2,5-8,10H2,1H3/t11-,12+,16+,19+/m1/s1 Y Key:RAUCDOKTMDOIPF-RYRUWHOVSA-N Y
NY (what is this?)

Noribogaine, or 12-hydroxyibogamine, is the principal psychoactive metabolite of the hallucinogenic drug ibogaine. It is thought to be involved in the antiaddictive effects of ibogaine-containing plant extracts, such as Tabernanthe iboga.

A recent study evaluated its effects on healthy volunteers at doses of 3–60 mg, finding no tolerability issues. A slow half-life of 28–49 hours was seen with large volume of distribution.

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 opioid receptors. It has greater affinity for each of the opioid receptors than does ibogaine.

Recently, 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. Moreover, due to its very low efficacy on the β-arrestin pathway, noribogaine blocked dynorphin A activation of the pathway (IC₅₀ = 1 μM) and hence functioned as an antagonist of it. The β-arrestin pathway is thought to be responsible for the dysphoric and effects of KOR activation, and its lack of activation by noribogaine may be the reason for the lack of dysphoric effects of the drug. This biased agonist/antagonist action of noribogaine at the KOR is unique to it relative to other iboga alkaloids and related compounds such as ibogaine and 18-methoxycoronaridine (18-MC). Moreover, it has been hypothesized that it may give noribogaine unique properties such that it may have the analgesic and antiaddictive effects of KOR agonists without the anxiogenic, dysphoric, or anhedonic effects that are typical of them.