Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents.
Martin E. Kuehne, Liwen He, Patrick A Jokiel, C J Pace, Mark W Fleck, Isabelle M Maisonneuve, Stanley D Glick, Jean M Bidlack
Journal of Medicinal Chemistry June 1, 2003 DOI: 10.1021/jm020562o (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Topics | Ibogaine |
| Keywords | Cell line Animals Humans Rats Substance-related disorders Morphine dependence Receptors, opioid Receptors, nicotinic Self administration Patch-clamp techniques Structure-activity relationship Stereoisomerism |
| Key points | The 15 synthesized congeners of 18-methoxycoronaridine showed relatively low opioid receptor activity, while their alpha3beta4 nicotinic acetylcholine receptor activity correlated with in vivo antiaddictive activity, suggesting this nicotinic receptor mediates the antiaddictive effects. |
Abstract
Variation of the methoxycarbonyl and C-18 substituents of the antiaddictive compound 18-methoxycoronaridine, and contraction of its isoquinuclidine ring segment, provided 15 congeners for SAR evaluation at opioid and alpha3beta4 nicotinic acetylcholine receptors. The opioid activities were relatively low, and the alpha3beta4 nicotinic acetylcholine receptor activities were found to correlate with in vivo antiaddictive activities.
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