Chemistry:Oxa-noribogaine

From HandWiki

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

Pharmacodynamics

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

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

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder". Pharmacology Biochemistry and Behavior 254. 2025. doi:10.1016/j.pbb.2025.174056. PMID 40588011. https://linkinghub.elsevier.com/retrieve/pii/S0091305725001030. Retrieved 31 July 2025. 
  2. ↑ 2.0 2.1 "Patent review of novel compounds targeting opioid use disorder (2018-2024)". Expert Opinion on Therapeutic Patents 35 (2): 165–180. February 2025. doi:10.1080/13543776.2024.2446230. PMID 39816001. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models". Nature Communications 15 (1). 2024. doi:10.1038/s41467-024-51856-y. PMID 39304653. Bibcode: 2024NatCo..15.8118H. 
  4. ↑ "Oxa-noribogaine reduces alcohol drinking through aversion learning and by altering glutamatergic activity in the mPFC". Research Square. March 2026. doi:10.21203/rs.3.rs-9103509/v1. PMID 41960323. 
  5. ↑ Kruegel AC (2015). Chemical and Biological Explorations of Novel Opioid Receptor Modulators (PhD thesis). Columbia University. doi:10.7916/D8V1242F.
  6. ↑ "Disrupting Substance Use Disorder: The Chemistry of Iboga Alkaloids". European Journal of Organic Chemistry 27 (36). 5 September 2024. doi:10.1002/ejoc.202400432. ISSN 1434-193X. PMID 40895173. 



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