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18-Methoxycoronaridine
Systematic (IUPAC) name
(–)-18-methoxycoronaridine
Identifiers
CAS number 308123-60-6
ATC code  ?
PubChem 10248465
ChemSpider 8423952
Chemical data
Formula C 22H28N2O3  
Mol. mass 368.47 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.  ?
Legal status
Routes  ?

(–)-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 and nicotine.[1]

18-MC is a selective α3β4 nicotinic antagonist and, in contrast to ibogaine, has no affinity at the α4β2 subtype nor at NMDA-channels nor at the serotonin transporter,[2] and has significantly reduced affinity for sodium channels and for the σ receptor, but retains modest affinity for the μ and κ opioid receptors.[3] The sites of action in the brain include the medial habenula, interpeduncular nucleus,[4][5][6] dorsolateral tegmentum and basolateral amygdala.[7] 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.[8]

18-MC has not yet been tested in humans. In 2002 the research team started trying to raise funds for human trials, but were unable to secure the estimated $5 million needed.[9] Efforts to raise funds for future trials are still ongoing.[1]

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,[10][11] although their effects on other targets such as the opioid receptors has not been assayed.

Iboga alkaloids.png

See also

References

  1. ^ S.D. Glick (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. doi:10.1016/0006-8993(96)00056-X. PMID 8782860.  
  2. ^ I.M. Maisonneuve (2003). "Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment". Pharmacol. Biochem. Behav. 75 (3): 607–18. doi:10.1016/S0091-3057(03)00119-9. PMID 12895678.  
  3. ^ 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.
  4. ^ 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. 2006 May 10;537(1-3):94-8. PMID 16626688
  5. ^ 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. 2007 Jul;61(7):547-60. PMID 17447255
  6. ^ 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. 2007 Jul;53(1):18-26. PMID 17544456
  7. ^ 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. 2008 Oct 1. [Epub ahead of print] PMID 18930043
  8. ^ Taraschenko OD, Rubbinaccio HY, Maisonneuve IM, Glick SD. 18-Methoxycoronaridine: a potential new treatment for obesity in rats? Psychopharmacology (Berlin). 2008 Aug 28. [Epub ahead of print] PMID 18751969
  9. ^ Addiction Treatment Strives for Legitimacy. Journal of the American Medical Association. 2002; 288: 3096-3101.
  10. ^ Kuehne ME, He L, Jokiel PA, Pace CJ, Fleck MW, Maisonneuve IM, Glick SD, Bidlack JM. Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents. Journal of Medicinal Chemistry. 2003 Jun 19;46(13):2716-30. PMID 12801235
  11. ^ 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. 2004 May 25;492(2-3):159-67. PMID 15178360

Further reading

  1. S.D. Glick (2006). "18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats". Eur. J. Pharmacol.. doi:10.1016/j.ejphar.2006.03.045. PMID 16626688.  
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