18-Methoxycoronaridine (18-MC) is a synthetic derivative of ibogaine that was developed in 1996 by researchers affiliated with Stanley D. Glick from the Albany Medical College and the Martin E. Kuehne from the University of Vermont.1 It was developed to avoid certain effects of ibogaine, which were considered undesirable, such as its oneirogenic effects, bradycardia (slowed heartbeat), tremors and ataxia.2
Structurally, ibogaine and 18-MC differ in that 18-MC does not have ibogaine’s 10-methoxy group and has a 16-carbomethoxy group, both of which are non-tremorigenic features.3 18-MC is so called because it also contains an 18-methoxy group.
Like ibogaine, administration of 18-MC results in long–lasting decreases in self–administration of ethanol, morphine, cocaine, nicotine and methamphetamine, as well as attenuation of opioid withdrawal symptoms. 18-MC’s probable lack of visions or “hallucinations” is due to its lack of effect on serotonin levels.4 Unlike ibogaine and its principal metabolite noribogaine, 18-MC does not increase expression of glial cell line-derived neurotrophic factor (GDNF) in a dopaminergic–like cell line.5 Some ibogaine advocates argue that 18-MC’s lack of GDNF expression, as well as probable lack of visions, indicates that ibogaine will remain more efficacious than 18-MC in treatment of substance use disorders.
On Jan. 3, 2013, Savant HWP, Inc. announced the receipt of a $6.5M (USD) grant from the United States National Institute on Drug Abuse (NIDA) for preclinical development of 18-MC for obesity and substance use disorders.6 On Feb. 7, 2014, Savant HWP filed an Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA) and expected to begin testing in humans in mid-2014.7 As of this writing, the IND is on hold pending further FDA review.8
Glick SD, Kuehne ME, Maisonneuve IM, Bandarage UK, Molinari HH. 18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats. Brain Research. May 1996;719(1):29-35. ↩
Glick SD, Maisonneuve IM, Szumlinski KK. 18-Methoxycoronaridine (18-MC) and ibogaine: comparison of antiaddictive efficacy, toxicity, and mechanisms of action. Annals of the New York Academy of Sciences. September 2000;914(1):369-386. ↩
Glick SD, Maisonneuve IM, Szumlinski KK. Mechanisms of Action of Ibogaine: Relevance to Putative Therapeutic Effects and Evelopment of a Safety Iboga Alkaloid Congener. The Alkaloids, Vol.56. 2001;39-53. ↩
Glick SD, et al. 2000. ↩
Carnicella S, He DY, Yowell QV, Glick SD, Ron D. Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration. Addiction Biology. October 2010;15(4):424-433. ↩
Funding announcement. ↩
Koberstein W. Savant HWP, A Biopharma Start-Up, Builds Its Business First And Decides On The Product Later. Life Science Leader. April 29, 2014. ↩