Nature-inspired indolyl-2-azabicyclo[2.2.2]oct-7-ene derivatives as promising agents for the attenuation of withdrawal symptoms: synthesis of 20-desethyl-20-hydroxymethyl-11-demethoxyibogaine.
Daniele Passarella, A Barilli, Simon M. N. Efange, E Elisabetsky, M B Leal, Giordano Lesma, V M Linck, Deborah C. Mash, Marisa Martinelli, I Peretto, Alessandra Silvani, Bruno Danieli
Natural Product Research July 10, 2006 DOI: 10.1080/14786410500160645 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14) |
| Topics | Ibogaine |
| Keywords | Addiction treatment Withdrawal management Substance abuse therapy Drug recovery Dependency treatment Addiction therapy Addiction medicine Addiction challenges Overcoming addiction Pharmaceutical research Compound identification Drug development New drug discovery Therapeutic innovation New treatments Creating treatments Receptor binding Drug action Neuropharmacology Mechanism of action Drug effects Dopamine receptors Serotonin receptors Opioid receptors Medicinal chemistry Drug design Synthetic chemistry Pharmaceutical chemistry Organic chemistry Precise chemical synthesis Ibogaine-inspired compounds Hydroxymethyl indolyl derivative |
| Citations | 4 |
| Key findings | A simplified ibogaine analogue, hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene, showed an antiwithdrawal effect in mice and a binding profile toward dopamine, serotonin, and opioid receptors. |
Abstract
Microwave assisted Diels-Alder cycloaddition of 5-Br-N-benzylpyridinone (2) with methyl acrylate is described to gain an easy access to 7-bromo-2-benzyl-3-oxo-2-aza-5 or 6-carbomethoxy bicyclo[2.2.2]oct-7-enes (3)-(6). The preparation of the ibogaine analogue 20-desethyl-(20-endo)-hydroxymethyl-11-demethoxyibogaine (17) is described by stereoselective hydrogenation of the C(7)-C(8) double bond. Biological evaluation showed an interesting in vitro binding profile toward dopamine transporter, serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14). The simplification of the ibogaine structure appears as a promising approach toward the design of compounds that could reduce the withdrawal symptoms.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 2
Cites 4
- NMDA antagonist properties of the putative antiaddictive drug, ibogaine. Journal of Pharmacology and Experimental Therapeutics November 1, 1995
- Ibogaine-like effects of noribogaine in rats. Brain Research March 25, 1996
- Modified ibogaine fragments: synthesis and preliminary pharmacological characterization of 3-ethyl-5-phenyl-1,2,3,4,5, 6-hexahydroazepino[4,5-b]benzothiophenes. Journal of Medicinal Chemistry November 5, 1998
- Ibogaine analogues. Synthesis and preliminary pharmacological evaluation of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes. Bioorganic & Medicinal Chemistry March 20, 2003