18-methoxycoronaridine

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Structural formula
Structure of 18-methoxycoronaridine
General
Surname 18-methoxycoronaridine
other names

(-) - 18-methoxycoronaridine

Molecular formula C 22 H 28 N 2 O 3
External identifiers / databases
CAS number 308123-60-6
PubChem 10248465
Wikidata Q200107
properties
Molar mass 368.47 g · mol -1
safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

18-Methoxycoronaridin ( 18-MC ) is a semisynthetic substance that is derived from the alkaloid coronaridin . Coronaridin is structurally related to ibogaine , both are indole alkaloids from the plant family Apocynaceae .

General

After Howard Lotsof made the discovery in 1962 that ibogaine was able to alleviate withdrawal symptoms in opiate addiction and also led to a reduction in the feeling of addiction ( substance craving ) - i.e. to a certain abstinence phenomenon - it was possible to scientifically confirm these initially anecdotal findings in the 1990s underpin. However, since ibogaine has serious side effects that prevent its possible approval as a drug, Stanley Glick and Martin Kuehne developed various derivatives in the mid-1990s, including 18-MC, in an effort to optimize ibogaine in its pharmacological profile and build on it, more precisely Gaining knowledge about the causal relationships of addiction . Other analogues were later synthesized and investigated, including 18-methylaminocoronaridine (18-MAC).

pharmacology

18-MC works similarly to ibogaine, but it has fewer side effects. In animal experiments it alleviates both the addictive strength ( substance cravings ) and withdrawal symptoms in opiate addiction. Interestingly, the addiction-relieving properties of 18-MC or ibogaine have also been demonstrated in a number of other substance-related dependencies, e.g. B. regarding nicotine , alcohol , amphetamine and cocaine .

18-MC and 18-MAC (18-methylaminocoronaridin) are non-competitive antagonists at a special nicotine receptor , of the subtype α 3 β 4 , with 18-MAC having the higher potency. This blockade correlates well with the observed anti-substance craving effects. However, selective α 3 β 4 blockers with high potency are still unknown to date. In contrast to ibogaine, these coronaridins have no affinity to the NMDA receptor and are otherwise significantly more selective in their binding profile.

In animal experiments, 18-MC reduced the self-administration of morphine and methamphetamine . Compared to 18-MC, 18-MAC is twice as effective in the morphine series, but less in methamphetamine. In contrast to ibogaine, the coronaryidins are neutral towards non-addictive substances.

An affinity chromatography method to effectively test substances for their affinity to the corresponding α 3 β 4 docking site ( screening ) was developed by Irving Wainer et al. A number of CNS -active substances seem to have a mild to moderate affinity , among them clozapine , SSRIs - antidepressants , methadone , dextromethorphan , laudanosine and mecamylamine (a former blood pressure drug).

See also

Individual evidence

  1. This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. a b c Pace, CJ. et al. (2004): Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration . In: Eur J Pharmacol . 492 (2-3), 159-67, PMID 15178360 .
  3. Panchal, V. et al. (2005): Attenuation of morphine withdrawal signs by intracerebral administration of 18-methoxycoronaridine . In: Eur J Pharmacol. 525 (1-3), 98-104, PMID 16289028 .
  4. Glick, SD. et al. (1999): (±) -18-Methoxycoronaridine: A Novel Iboga Alkaloid Congener Having Potential Anti-Addictive Efficacy . In: CNS Drug Reviews 5 (1), 27-42; doi : 10.1111 / j.1527-3458.1999.tb00084.x .
  5. R. Moaddel, K. Jozwiak, R. Yamaguchi, C. Cobello, K. Whittington, TK Sarkar, S. Basak, IW Wainer: On-line screening of conformationally constrained nicotines and anabasines for agonist activity at the alpha3beta4- and alpha4beta2 -nicotinic acetylcholine receptors using immobilized receptor-based liquid chromatographic stationary phases. In: Journal of Chromatography B . Volume 813, number 1-2, December 2004, pp. 235-240, doi : 10.1016 / j.jchromb.2004.09.042 , PMID 15556538 .
  6. Jozwiak, K. et al. (2004): Interaction of noncompetitive inhibitors with an immobilized α3β4 nicotinic acetylcholine receptor investigated by affinity chromatography, quantitative-structure activity relationship analysis, and molecular docking . In: J Med Chem. 47 (16), 4008-4021, PMID 15267239 .