Oxa-noribogaine

Oxa-noribogaine
Clinical data
Other names	Oxanoribogaine; Oxa-noriboga; 16-Oxanoribogaine; Furanyl-noribogaine; 12-Hydroxy-16-oxaibogamine; 16-Oxaibogamin-12-ol
Drug class	Atypical κ-opioid receptor partial agonist
Identifiers
	IUPAC name (1R,15S,17S)-17-ethyl-3-oxa-13-azapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4(9),5,7-tetraen-7-ol;
PubChem CID	171470286;
Chemical and physical data
Formula	C19H23NO2
Molar mass	297.398 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC[C@H]1C[C@H]2C[C@@H]3C1N(C2)CCC4=C3OC5=C4C=C(C=C5)O;
	InChI InChI=1S/C19H23NO2/c1-2-12-7-11-8-16-18(12)20(10-11)6-5-14-15-9-13(21)3-4-17(15)22-19(14)16/h3-4,9,11-12,16,18,21H,2,5-8,10H2,1H3/t11-,12-,16+,18?/m0/s1; Key:FZMCHQSKCBWMJA-UPHWXITMSA-N;

Oxa-noribogaine is an atypical κ-opioid receptor agonist of the "oxa-iboga" family and a synthetic benzofuran analogue of noribogaine.^[1]^[2]^[3] Although it still binds to hERG with similar avidity as noribogaine, it appears to be devoid of the proarrhythmic side effects of noribogaine.^[1]^[3]

Pharmacology

Oxa-noribogaine acts as an atypical κ-opioid receptor (KOR) partial agonist similarly to noribogaine but shows dramatically increased potency and selectivity compared to noribogaine (EC₅₀Tooltip half-maximal effective concentration = 43 nM vs. 6,100 nM, respectively; 142-fold difference).^[3] It produces analgesic effects in animals, but unlike conventional KOR agonists, does not produce aversive or pro-depressive effects.^[1]^[3] The drug induces a robust KOR-dependent increase in GDNF levels in the ventral tegmental area (VTA) and medial prefrontal cortex (mPFC).^[1]^[3] After a single dose or short-term treatment, oxa-noribogaine induces long-lasting suppression of opioid drug-seeking behavior in rodent relapse models.^[1]^[3] It also counteracts persistent opioid-induced hyperalgesia.^[3] In addition, oxa-noribogaine decreases alcohol consumption in rodents.^[4]

Oxa-noribogaine was first described in the scientific literature in 2015.^[5] Subsequently, it was further described in 2024.^[1]^[6]^[2]^[3]

1 2 3 4 5 6 Liu-Chen LY, Huang P (2025). "KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder". Pharmacology Biochemistry and Behavior. 254 174056. doi:10.1016/j.pbb.2025.174056. PMID 40588011. Retrieved 31 July 2025.
1 2 Obeng S, McMahon LR, Ofori E (February 2025). "Patent review of novel compounds targeting opioid use disorder (2018-2024)". Expert Opinion on Therapeutic Patents. 35 (2): 165–180. doi:10.1080/13543776.2024.2446230. PMID 39816001.
1 2 3 4 5 6 7 8 Havel V, Kruegel AC, Bechand B, McIntosh S, Stallings L, Hodges A, et al. (2024). "Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models". Nature Communications. 15 (1) 8118. Bibcode:2024NatCo..15.8118H. doi:10.1038/s41467-024-51856-y. PMC 11415492. PMID 39304653.
↑ Meinhardt M, Skorodumov I, Walter F, Akan M, Buchborn T, Prieult YL, et al. (March 2026). "Oxa-noribogaine reduces alcohol drinking through aversion learning and by altering glutamatergic activity in the mPFC". Res Sq. doi:10.21203/rs.3.rs-9103509/v1. PMC 13060505. PMID 41960323.
↑ Kruegel AC (2015). Chemical and Biological Explorations of Novel Opioid Receptor Modulators (PhD thesis). Columbia University. doi:10.7916/D8V1242F.
↑ Hughes AJ, Hamelink CR, Townsend SD (5 September 2024). "Disrupting Substance Use Disorder: The Chemistry of Iboga Alkaloids". European Journal of Organic Chemistry e202400432. doi:10.1002/ejoc.202400432. ISSN 1434-193X.