18-Methoxycoronaridine

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18-Methoxycoronaridine
Clinical data
Other names
  • (−)-18-methoxycoronaridine
  • Zolunicant
Routes of
administration
Oral
Legal status
Legal status
Identifiers
  • methyl (1S,15R,17R,18S)-17-(2-methoxyethyl)-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4,6,8-tetraene-1-carboxylate
JSmol)
  • COCC[C@H]1C[C@@H]2C[C@@]3([C@H]1N(C2)CCc4c3[nH]c5c4cccc5)C(=O)OC
  • InChI=1S/C22H28N2O3/c1-26-10-8-15-11-14-12-22(21(25)27-2)19-17(7-9-24(13-14)20(15)22)16-5-3-4-6-18(16)23-19/h3-6,14-15,20,23H,7-13H2,1-2H3/t14-,15+,20+,22-/m1/s1 ☒N
  • Key:DTJQBBHYRQYDEG-SVBQBFEESA-N ☒N
 ☒NcheckY (what is this?)  (verify)

18-Methoxycoronaridine (18-MC, or MM-110), also known as zolunicant, is a derivative of ibogaine invented in 1996 by the research team around the pharmacologist Stanley D. Glick from the Albany Medical College and the chemists Upul K. Bandarage and Martin E. Kuehne from the University of Vermont. In animal studies it has proved to be effective at reducing self-administration of morphine, cocaine, methamphetamine, nicotine and sucrose.[1][2] It has also been shown to produce anorectic effects in obese rats, most likely due to the same actions on the reward system which underlie its anti-addictive effects against drug addiction.[3]

18-MC was in the early stages of human testing by the California-based drug development company Savant HWP before being acquired by MindMed, a Canadian pharmaceutical company newly listed on the NASDAQ in April 2021.[4][5] In 2002 the research team began raising funds for human trials, but were unable to secure the estimated $5 million needed.[6] In 2010, Obiter Research, a chemical manufacturer in Champaign, Illinois, signed a patent license with Albany Medical College and the University of Vermont, allowing them the right to synthesize and market 18-MC and other congeners. In 2012 the National Institute on Drug Abuse gave a $6.5 million grant to Savant HWP for human trials.[5] In 2017 it went into Phase-II trials in Brazil for treatment of Leishmaniasis at the Evandro Chagas Institute,[7] but not for approval for use as a treatment for drug addiction. A phase 2a study of MM-110 treatment in patients experiencing opioid withdrawal is set to commence in Q2 2022.[8]

Pharmacology

18-MC is a

medial habenula, interpeduncular nucleus,[12][13][14] dorsolateral tegmentum and basolateral amygdala.[15] (±)-18-MC competitively inhibits α9α10 nAChRs with potencies higher than that at α3β4 and α4β2 nAChRs and directly blocks CaV2.2.[16]

Chemistry

Derivatives

A number of derivatives of 18-MC have been developed, with several of them being superior to 18-MC itself, the methoxyethyl congener

α3β4 nicotinic acetylcholine antagonists, with little or no effect on NMDA receptors.[17][18]

See also

References

  1. S2CID 6178161
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  4. ^ Mindmed Acquires Opioid Addiction Drug Candidate Based on the Natural Psychedelic Ibogaine newswire.ca September 16, 2019.
  5. ^ a b Albany Med scientist closer to addiction drug success timesunion.com June 27, 2014.
  6. ^ Addiction Treatment Strives for Legitimacy. Journal of the American Medical Association. 2002; 288: 3096-3101.
  7. ^ "Phase 2 Trial to Evaluate 18-Methoxycoronaridine Efficacy, Safety and Tolerability in Cutaneous Leishmaniasis Patients". ClinicalTrials.gov. Retrieved 19 February 2020.
  8. ^ "Opioid Use Disorder: Zolunicant's Potential for Unmet Treatment Needs". MindMed.co. 20 May 2022. Retrieved 23 May 2022.
  9. S2CID 26758480
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  11. ^ Glick SD, Maisonneuve IM, Hough LB, Kuehne ME, Bandarage UK. (±)-18-Methoxycoronaridine: A Novel Iboga Alkaloid Congener Having Potential Anti-Addictive Efficacy. CNS Drug Reviews 1999;5(1):27-42.
  12. PMID 16626688
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