18-Methoxycoronaridine

Chemical compound changed changed 477209336 Zolunicant 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 18-Methoxycoronaridine.svg skin-invert-image 225px 18-methoxycoronaridine 3D BS.png bg-transparent 225px IND (filed 2/9/2014) Oral racemic correct CAS 308123-60-6 correct CAS 188125-42-0 changed FDA KX8NQX91Z8 correct FDA VG463BM9RL 10248465 changed chemspider 24721799 18-MC; Zolunicant; MM-110; MM110 22 28 2 3 COCC[C@H]1C[C@@H]2C[C@@]3([C@H]1N(C2)CCc4c3[nH]c5c4cccc5)C(=O)OC changed chemspider 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 changed chemspider DTJQBBHYRQYDEG-SVBQBFEESA-N 18-Methoxycoronaridine (18-MC; developmental code name MM-110), also known as zolunicant (INN International Nonproprietary Name), 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. 18-MC was originally developed by Savant HWP and later acquired by MindMed in 2019 for development as a treatment for opioid use disorder.Mindmed Acquires Opioid Addiction Drug Candidate Based on the Natural Psychedelic Ibogaine https://www.newswire.ca/news-releases/mindmed-acquires-opioid-addiction-drug-candidate-based-on-the-natural-psychedelic-ibogaine-891112447.html 2025-11-25 www.newswire.ca A Phase 1 trial in healthy volunteers was completed in 2022 with favorable safety and tolerability.MindMed Reports Topline Data From Phase 1 Trial of MM-110 in Development for the Treatment of Opioid Withdrawal - MindMed https://mindmed.co/news/press-release/mindmed-reports-topline-data-from-phase-1-trial-of-mm-110-in-development-for-the-treatment-of-opioid-withdrawal/ https://web.archive.org/web/20220703234333/https://mindmed.co/news/press-release/mindmed-reports-topline-data-from-phase-1-trial-of-mm-110-in-development-for-the-treatment-of-opioid-withdrawal/ 2025-11-25 2022-07-03 Due to strategic reprioritization, MindMed discontinued active development of MM-110 in 2023 and has been seeking non-dilutive funding or partners to potentially restart the program; as of 2025 the program remains shelved.MindMed Investor Presentation live https://mindmed.co/wp-content/uploads/2023/06/MindMed-Investor-Day-2023-Presentation.pdf https://web.archive.org/web/20230930231631/https://mindmed.co/wp-content/uploads/2023/06/MindMed-Investor-Day-2023-Presentation.pdf 2023-09-30FORM 10-K - Mind Medicine (MindMed) Inc. https://ir.mindmed.co/sec-filings/all-sec-filings/content/0000950170-25-034176/0000950170-25-034176.pdf https://web.archive.org/web/20250315034141/https://ir.mindmed.co/sec-filings/all-sec-filings/content/0000950170-25-034176/0000950170-25-034176.pdf 2025-03-15 A separate Phase 2 trial in Brazil for cutaneous leishmaniasis (initiated 2017) has unknown status with no published results.ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03084952 2025-11-25 clinicaltrials.gov Pharmacology 18-MC is a α3β4 nicotinic antagonist and, in contrast to ibogaine, has no affinity at the α4β2 subtype nor at NMDA-channels nor at the serotonin transporter, Maisonneuve IM, Glick SD Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment Pharmacology, Biochemistry, and Behavior 75 3 607–18 June 2003 12895678 10.1016/S0091-3057(03)00119-9 26758480 and has significantly reduced affinity for sodium channels and for the σ receptor, but retains modest affinity for μ-opioid receptors where it acts as an agonist, Antonio T, Childers SR, Rothman RB, Dersch CM, King C, Kuehne M, Bornmann WG, Eshleman AJ, Janowsky A, Simon ER, Reith ME, Alper K 6 Effect of Iboga alkaloids on μ-opioid receptor-coupled G protein activation PLOS ONE 8 10 e77262 2013 24204784 3818563 10.1371/journal.pone.0077262 2013PLoSO...877262A free and κ-opioid receptors.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. The sites of action in the brain include the medial habenula, interpeduncular nucleus, Glick SD, Ramirez RL, Livi JM, Maisonneuve IM 18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats European Journal of Pharmacology 537 1–3 94–8 May 2006 16626688 10.1016/j.ejphar.2006.03.045 Taraschenko OD, Shulan JM, Maisonneuve IM, Glick SD 18-MC acts in the medial habenula and interpeduncular nucleus to attenuate dopamine sensitization to morphine in the nucleus accumbens Synapse 61 7 547–60 July 2007 17447255 10.1002/syn.20396 2252348 Taraschenko OD, Rubbinaccio HY, Shulan JM, Glick SD, Maisonneuve IM Morphine-induced changes in acetylcholine release in the interpeduncular nucleus and relationship to changes in motor behavior in rats Neuropharmacology 53 1 18–26 July 2007 17544456 2025684 10.1016/j.neuropharm.2007.04.010 dorsolateral tegmentum and basolateral amygdala. Glick SD, Sell EM, Maisonneuve IM Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration European Journal of Pharmacology 599 1–3 91–5 December 2008 18930043 2600595 10.1016/j.ejphar.2008.09.038 (±)-18-MC competitively inhibits α9α10 nAChRs with potencies higher than that at α3β4 and α4β2 nAChRs and directly blocks CaV2.2.Arias HR, Tae HS, Micheli L, Yousuf A, Ghelardini C, Adams DJ, Di Cesare Mannelli L Coronaridine congeners decrease neuropathic pain in mice and inhibit α9α10 nicotinic acetylcholine receptors and CaV2.2 channels Neuropharmacology 175 108194 September 2020 32540451 10.1016/j.neuropharm.2020.108194 https://ro.uow.edu.au/ihmri/1536 2158/1213504 219705597 free 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 ME-18-MC being more potent than 18-MC with similar efficacy, and the methylamino analogue 18-MAC being more effective than 18-MC with around the same potency. These compounds were also found to act as selective α3β4 nicotinic acetylcholine antagonists, with little or no effect on NMDA receptors. Kuehne ME, He L, Jokiel PA, Pace CJ, Fleck MW, Maisonneuve IM, Glick SD, Bidlack JM 6 Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents Journal of Medicinal Chemistry 46 13 2716–30 June 2003 12801235 10.1021/jm020562o Pace CJ, Glick SD, Maisonneuve IM, He LW, Jokiel PA, Kuehne ME, Fleck MW Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration European Journal of Pharmacology 492 2–3 159–67 May 2004 15178360 10.1016/j.ejphar.2004.03.062 class=skin-invert-image|500px See also Coronaridine Ibogaine Noribogaine Voacangine References 2 Category:Anti-addictive drugs Category:Drug rehabilitation Category:Tabernanthe iboga Category:Nicotinic antagonists Category:Kappa-opioid receptor agonists Category:Mu-opioid receptor antagonists Category:Opioid modulators