Modified ibogaine fragments: synthesis and preliminary pharmacological characterization of 3-ethyl-5-phenyl-1,2,3,4,5, 6-hexahydroazepino[4,5-b]benzothiophenes.
Simon M. N. Efange, Deborah C. Mash, A B Khare, Q Ouyang
Journal of Medicinal Chemistry November 5, 1998 DOI: 10.1021/jm980156y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Qualitative Peer reviewed |
|---|---|
| Topics | Ibogaine Serotonin |
| Keywords | Drug discovery New compounds Novel compounds Synthesized Derivatives Fragments Medicinal chemistry Drug development Compound synthesis Addiction treatment Substance abuse therapy Addiction therapy Therapeutic applications Ibogaine research Neuropharmacology Dopamine transporters Serotonin transporters Dopamine d3 receptors Receptor binding Transporter modulation Neurotransmitter systems Potency |
| Citations | 33 |
| Key findings | All five phenyl-substituted derivatives of the ibogaine fragment displayed 8-10-fold higher affinity at the dopamine transporter than ibogaine and noribogaine. |
Abstract
Five phenyl-substituted derivatives and analogues of 1,2,3,4,5, 6-hexahydroazepino[4,5-b]indole, 5, a major fragment of ibogaine (1), were synthesized and tested for binding to monoamine transporters, the NMDA receptor-coupled cation channel, and dopamine and opioid receptors. All five derivatives, 9 and 17a-d, displayed 8-10-fold higher affinity at the DA transporter than ibogaine and noribogaine (4). At the serotonin transporter, two compounds (9 and 17a) exhibited higher potency than ibogaine, while the rest had weaker binding affinities than the lead compound. In keeping with their structural similarity to ibogaine, all five compounds displayed weak to poor affinity for dopamine D1 and D2 receptors. However, two compounds, 17a,c, demonstrated moderate binding affinities at dopamine D3 receptors. All five compounds displayed weak to poor affinities for mu and kappa opioid receptors and for the NMDA receptor-coupled cation channel. Despite the qualitative differences, derivatives and analogues of 5may serve as useful substitutes for ibogaine.
Comparable studies
Other experimental studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. In vitro (SERT) | 2007 | Laboratory study | |
| Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. | 1992 | Laboratory study | |
| The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. | 2012 | Experimental study | |
| Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. | 1995 | Experimental study | |
| Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity. | 1995 | Laboratory study |
Citations in the library
Cited by 6
- IUPHAR - invited review - Ibogaine - A legacy within the current renaissance of psychedelic therapy. Pharmacological Research April 1, 2023
- Ibogaine analogues. Synthesis and preliminary pharmacological evaluation of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes. Bioorganic & Medicinal Chemistry March 20, 2003
- Reactivity of the Iboga Skeleton: Oxidation Study of Ibogaine and Voacangine. Journal of Natural Products June 23, 2023
- 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. Natural Product Research July 10, 2006
- The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs. Natural Product Reports March 4, 2021
and 1 more in the library
Cites 22
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- 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. Brain Research September 19, 1994
- Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Research February 7, 1992
- Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats. Pharmacology, Biochemistry, and Behavior November 1, 1995
- Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Neuropharmacology May 1, 1992
and 17 more in the library