Oxa-noribogaine
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| Other names | Oxanoribogaine; Oxa-noriboga; 16-Oxanoribogaine; Furanyl-noribogaine; 12-Hydroxy-16-oxaibogamine; 16-Oxaibogamin-12-ol |
| Drug class | κ-Opioid receptor agonist |
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| PubChem CID | |
| Chemical and physical data | |
| Formula | C19H23NO2 |
| Molar mass | 297.398 g·mol−1 |
| 3D model (JSmol) | |
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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
[edit]Pharmacodynamics
[edit]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 (EC50 = 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]
History
[edit]Oxa-noribogaine was first described in the scientific literature in 2015.[5] Subsequently, it was further described in 2024.[1][6][2][3]
See also
[edit]References
[edit]- 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". Research Square. 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. 27 (36) e202400432. doi:10.1002/ejoc.202400432. ISSN 1434-193X. PMC 12393092. PMID 40895173.