World Library  
Flag as Inappropriate
Email this Article

18-Methoxycoronaridine

Article Id: WHEBN0004573749
Reproduction Date:

Title: 18-Methoxycoronaridine  
Author: World Heritage Encyclopedia
Language: English
Subject: Eseroline, List of opioids, Cyclazocine, Nicotinic antagonist, Noribogaine
Collection: Drug Rehabilitation, Iboga, Kappa Agonists, Nicotinic Antagonists, Opioid Antagonists
Publisher: World Heritage Encyclopedia
Publication
Date:
 

18-Methoxycoronaridine

18-Methoxycoronaridine
Systematic (IUPAC) name
(–)-18-methoxycoronaridine
Clinical data
Legal status
  • US IND filed 2/9/2014
Routes oral
Identifiers
CAS number  N
ATC code ?
PubChem
ChemSpider  YesY
Chemical data
Formula C22H28N2O3 
Mol. mass 368.47 g/mol
 N   

(–)-18-Methoxycoronaridine (18-MC) 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 chemist 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] 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,[3] 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 antagonist,[4] and κ-opioid receptors.[5] The sites of action in the brain include the medial habenula, interpeduncular nucleus,[6][7][8] dorsolateral tegmentum and basolateral amygdala.[9] 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.[10]

18-MC is in the early stages of human testing by Savant HWP.[11] In 2002 the research team started trying to raise funds for human trials, but were unable to secure the estimated $5 million needed.[12] In January 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. National Institute on Drug Abuse gave a $6.5 million grant in 2012 to California based drug developer company Savant HWP for the human trials.[11]

A number of derivatives of 18-MC have also been developed, with several of them being superior to 18-MC itself, the methoxyethyl congener ME-18-MC being more potent than 18-MC but with similar efficacy, and the methylamino analogue 18-MAC being more effective than 18-MC but 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.[13][14]

See also

References

  1. ^ S.D. Glick; Kuehne, ME; Maisonneuve, IM; Bandarage, UK; Molinari, HH (1996). "18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats". Brain Res. 719 (1–2): 29–35.  
  2. ^ Glick, Stanley D.; Sell, Elizabeth M.; Maisonneuve, Isabelle M. (2008). "Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration". European Journal of Pharmacology 599 (1–3): 91–5.  
  3. ^ I.M. Maisonneuve; Glick, SD (2003). "Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment". Pharmacol. Biochem. Behav. 75 (3): 607–18.  
  4. ^ Antonio T, Childers SR, Rothman RB, et al. (2013). "Effect of Iboga alkaloids on µ-opioid receptor-coupled G protein activation". PLoS ONE 8 (10): e77262.  
  5. ^ 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.
  6. ^ Glick, SD; Ramirez, RL; Livi, JM; Maisonneuve, IM (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.  
  7. ^ Taraschenko, OD; Shulan, JM; Maisonneuve, IM; Glick, SD (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.  
  8. ^ Taraschenko, OD; Rubbinaccio, HY; Shulan, JM; Glick, SD; Maisonneuve, IM (2007). "Morphine-induced changes in acetylcholine release in the interpeduncular nucleus and relationship to changes in motor behavior in rats". Neuropharmacology 53 (1): 18–26.  
  9. ^ Glick, SD; Sell, EM; Maisonneuve, IM (2008). "Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration". European Journal of Pharmacology 599 (1–3): 91–5.  
  10. ^ Taraschenko, OD; Rubbinaccio, HY; Maisonneuve, IM; Glick, SD (2008). "18-methoxycoronaridine: a potential new treatment for obesity in rats?". Psychopharmacology 201 (3): 339–50.  
  11. ^ a b Albany Med scientist closer to addiction drug success timesunion.com June 27, 2014.
  12. ^ Addiction Treatment Strives for Legitimacy. Journal of the American Medical Association. 2002; 288: 3096-3101.
  13. ^ Kuehne, ME; He, L; Jokiel, PA; Pace, CJ; Fleck, MW; Maisonneuve, IM; Glick, SD; Bidlack, JM (2003). "Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents". Journal of Medical Chemistry 46 (13): 2716–30.  
  14. ^ Pace, CJ; Glick, SD; Maisonneuve, IM; He, LW; Jokiel, PA; Kuehne, ME; Fleck, MW (2004). "Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration". European Journal of Pharmacology 492 (2–3): 159–67.  

Further reading

  1. S.D. Glick; Ramirez, RL; Livi, JM; Maisonneuve, IM (2006). "18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats". Eur. J. Pharmacol. 537 (1–3): 94–8.  
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.