18-Methoxycoronaridine (18-MC; developmental code name MM-110), also known as zolunicant (INNTooltip 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. In animal studies it has proven 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]
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.[17][18]
^Maisonneuve IM, Glick SD (June 2003). "Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment". Pharmacology, Biochemistry, and Behavior. 75 (3): 607–18. doi:10.1016/S0091-3057(03)00119-9. PMID12895678. S2CID26758480.
^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.
^Glick SD, Ramirez RL, Livi JM, Maisonneuve IM (May 2006). "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. doi:10.1016/j.ejphar.2006.03.045. PMID16626688.
^Taraschenko OD, Shulan JM, Maisonneuve IM, Glick SD (July 2007). "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. doi:10.1002/syn.20396. PMID17447255. S2CID2252348.