18-Methoxycoronaridine


18-Methoxycoronaridine, 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 proven to be effective at reducing self-administration of morphine, cocaine, methamphetamine, nicotine, and sucrose. 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.
18-MC was originally developed by Savant HWP and later acquired by MindMed in 2019 for development as a treatment for opioid use disorder. A Phase 1 trial in healthy volunteers was completed in 2022 with favorable safety and tolerability. 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. A separate Phase 2 trial in Brazil for cutaneous leishmaniasis has unknown status with no published results.

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, 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, and κ-opioid receptors. The sites of action in the brain include the medial habenula, interpeduncular nucleus, dorsolateral tegmentum and basolateral amygdala. -18-MC competitively inhibits α9α10 nAChRs with potencies higher than that at α3β4 and α4β2 nAChRs and directly blocks CaV2.2.

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.