Tabernanthalog

Last updated
Tabernanthalog
Tabernanthalog.svg
Tabernanthalog.png
Clinical data
Other namesTBG; DLX-007; DLX007
Drug class Non-selective serotonin receptor modulator; Non-hallucinogenic serotonin 5-HT2A receptor partial agonist
ATC code
  • None
Identifiers
  • 8-methoxy-3-methyl-2,4,5,6-tetrahydro-1H-azepino[4,5-b]indole
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
Formula C14H18N2O
Molar mass 230.311 g·mol−1
3D model (JSmol)
  • CN1CCC2=C(CC1)NC3=C2C=CC(=C3)OC
  • InChI=1S/C14H18N2O/c1-16-7-5-12-11-4-3-10(17-2)9-14(11)15-13(12)6-8-16/h3-4,9,15H,5-8H2,1-2H3
  • Key:FNGNYGCPNKZYOG-UHFFFAOYSA-N

Tabernanthalog (TBG; developmental code name DLX-007) is a non-selective serotonin receptor modulator and non-psychedelic psychoplastogen of the ibogalog group related to the iboga alkaloid tabernanthine but with a simplified chemical structure. [1] [2] It was developed by David E. Olson and colleagues at the University of California, Davis. [2] The drug is being developed by Delix Therapeutics as a potential pharmaceutical drug for treatment of neuropsychiatric disorders. [3] [4]

Contents

Pharmacology

Tabernanthalog activities
Target Affinity (Ki, nM)
5-HT1A 39% BI @ 10 μM
14,600 (EC50 Tooltip half-maximal effective concentration)
95% (Emax Tooltip maximal efficacy)
5-HT1B 66% BI @ 10 μM
34 (EC50)
87% (Emax)
5-HT1D ND (Ki)
2,180 (EC50)
76% (Emax)
5-HT1E ND (Ki)
2,784 (EC50)
117% (Emax)
5-HT1F ND (Ki)
40 (EC50)
64% (Emax)
5-HT2A 4,440 (Ki)
57% BI @ 10 μM
147–4,570 (EC50)
8–91% (Emax)
5-HT2B 439 (Ki)
86% BI @ 10 μM
2,827 or IA (EC50)
46% or IA (Emax)
5-HT2C 28,590 (Ki)
99% BI @ 10 μM
13–69 (EC50)
21–99% (Emax)
5-HT3 14% BI @ 10 μM
5-HT4 ND (Ki)
>10,000 (EC50)
5-HT5A ND (Ki)
>10,000 (EC50)
5-HT6 ND (Ki)
132–214 (EC50)
88–133% (Emax)
5-HT7 ND (Ki)
>10,000 (EC50)
α1A–α1D 15–20% BI @ 10 μM
α2A 81% BI @ 10 μM
α2B 27% BI @ 10 μM
α2C ND
β1–β2 9% BI @ 10 μM
D1, D2 3–18% BI @ 10 μM
D3–D5 ND
H1 35% BI @ 10 μM
H2 –12% BI @ 10 μM
H3, H4 ND
M1–M4 2–18% BI @ 10 μM
M5 ND
nACh Tooltip Nicotinic acetylcholine receptor16–19% BI @ 10 μM
I1, I2 ND
σ1, σ2 ND
MOR Tooltip μ-Opioid receptor17% BI @ 10 μM
IA (EC50)
DOR Tooltip δ-Opioid receptor14% BI @ 10 μM
IA (EC50)
KOR Tooltip κ-Opioid receptor7% BI @ 10 μM
>10,000 (EC50)
NMDAR Tooltip N-Methyl-D-aspartate receptor0–3% BI @ 10 μM (rat)
TAAR1 Tooltip Trace amine-associated receptor 1ND
SERT Tooltip Serotonin transporter88% BI @ 10 μM
600 (IC50 Tooltip half-maximal inhibitory concentration)
NET Tooltip Norepinephrine transporterND (Ki)
5,400 (IC50)
DAT Tooltip Dopamine transporterND (Ki)
65,000 (IC50)
VMAT Tooltip Vesicular monoamine transporter10% BI @ 10 μM
MAO-A Tooltip Monoamine oxidase A66% BI @ 10 μM
15,100 (IC50)
MAO-B Tooltip Monoamine oxidase B16% BI @ 10 μM
28% FI @ 100 μM
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [2] [5] [1] [6] [7] [8]

Tabernanthalog is a non-selective and non-psychedelic serotonin receptor modulator, including acting as an agonist of the serotonin 5-HT1B, 5-HT1F, 5-HT2A, 5-HT2C, and 5-HT6 receptors and as an agonist or antagonist of the serotonin 5-HT2B receptor. [2] [5] [7] It also shows significant binding to the serotonin transporter (SERT) (acting as a serotonin reuptake inhibitor), the α2A-adrenergic receptor, and monoamine oxidase A (MAO-A). [2] In contrast to iboga alkaloids like ibogaine and noribogaine, tabernanthalog showed negligible interactions with opioid receptors, the NMDA receptor, and certain nicotinic acetylcholine receptors. [2] However, in subsequent research, it weakly inhibited certain nicotinic acetylcholine receptors, as well as, to a much lesser extent, the GABAA receptor. [9] Tabernanthalog was found to be 100-fold less potent at the hERG antitarget compared to ibogaine, and hence is thought to have a much lower potential for cardiotoxicity. [2]

Tabernanthalog did not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and hence appears to be non-hallucinogenic. [2] However, it was found to promote structural neuroplasticity (i.e., to act as a psychoplastogen), reduce drug-seeking behavior, and produce antidepressant-like effects. [2] [10] [11] [12] It has also been shown that it reduces motivation for heroin and alcohol in rodents. [12]

See also

References

  1. 1 2 Sharp T, Ippolito A (May 2025). "Neuropsychopharmacology of hallucinogenic and non-hallucinogenic 5-HT2A receptor agonists". Br J Pharmacol. doi:10.1111/bph.70050. PMID   40405723.
  2. 1 2 3 4 5 6 7 8 9 Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, et al. (January 2021). "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature. 589 (7842): 474–479. Bibcode:2021Natur.589..474C. doi:10.1038/s41586-020-3008-z. PMC   7874389 . PMID   33299186.
  3. ↑ "DLX 7". AdisInsight. 28 May 2025. Retrieved 31 July 2025.
  4. ↑ Grace B (6 March 2021). "Can we take the high out of psychedelics?". Wired. Retrieved 12 July 2022.
  5. 1 2 Arias HR, Micheli L, Rudin D, Bento O, Borsdorf S, Ciampi C, Marin P, Ponimaskin E, Manetti D, Romanelli MN, Ghelardini C, Liechti ME, Di Cesare Mannelli L (August 2024). "Non-hallucinogenic compounds derived from iboga alkaloids alleviate neuropathic and visceral pain in mice through a mechanism involving 5-HT2A receptor activation". Biomed Pharmacother. 177: 116867. doi:10.1016/j.biopha.2024.116867. PMID   38889634.
  6. ↑ Ippolito A, Vasudevan S, Hurley S, Gilmour G, Westhorpe F, Churchill G, Sharp T (June 2025). "Evidence that 5-HT2A receptor signalling efficacy and not biased agonism differentiates serotonergic psychedelic from non-psychedelic drugs". Br J Pharmacol. doi:10.1111/bph.70109. PMID   40545270.
  7. 1 2 Arias HR, Rudin D, Luethi D, Valenta J, Leśniak A, Czartoryska Z, Olejarz-Maciej A, Doroz-Płonka A, Manetti D, De Deurwaerdère P, Romanelli MN, Handzlik J, Liechti ME, Chagraoui A (January 2025). "The psychoplastogens ibogaminalog and ibogainalog induce antidepressant-like activity in naïve and depressed mice by mechanisms involving 5-HT2A receptor activation and serotonergic transmission". Prog Neuropsychopharmacol Biol Psychiatry. 136: 111217. doi:10.1016/j.pnpbp.2024.111217. PMID   39662723.
  8. ↑ Arias HR, Micheli L, Jensen AA, Galant S, Vandermoere F, Venturi D, Manetti D, Romanelli MN, Ghelardini C, Marin P, Di Cesare Mannelli L (March 2025). "Ibogalogs decrease neuropathic pain in mice through a mechanism involving crosstalk between 5-HT2A and mGlu2 receptors". Biomed Pharmacother. 184: 117887. doi:10.1016/j.biopha.2025.117887. PMID   39938347.
  9. ↑ Tae HS, Ortells MO, Yousuf A, Xu SQ, Akk G, Adams DJ, Arias HR (May 2024). "Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABAA receptor and CaV2.2 channel". Biochem Pharmacol. 223: 116183. doi:10.1016/j.bcp.2024.116183. PMC   11151864 . PMID   38580167.
  10. ↑ Lu J, Tjia M, Mullen B, Cao B, Lukasiewicz K, Shah-Morales S, et al. (November 2021). "An analog of psychedelics restores functional neural circuits disrupted by unpredictable stress". Molecular Psychiatry. 26 (11): 6237–6252. doi:10.1038/s41380-021-01159-1. PMC   8613316 . PMID   34035476.
  11. ↑ Peters J, Olson DE (2021-07-20). "Engineering Safer Psychedelics for Treating Addiction". Neuroscience Insights. 16: 26331055211033847. doi:10.1177/26331055211033847. PMC   8295933 . PMID   34350400.
  12. 1 2 Heinsbroek JA, Giannotti G, Bonilla J, Olson DE, Peters J (June 2023). "Tabernanthalog Reduces Motivation for Heroin and Alcohol in a Polydrug Use Model". Psychedelic Medicine. 1 (2): 111–119. doi:10.1089/psymed.2023.0009. PMC   10286262 . PMID   37360328.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.