Tabernanthalog

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Tabernanthalog
Tabernanthalog.svg
Ball and Stick 3D representation of a tabernanthalog molecule Tabernanthalog.png
Ball and Stick 3D representation of a tabernanthalog molecule
Names
IUPAC name
8-methoxy-3-methyl-2,4,5,6-tetrahydro-1H-azepino[4,5-b]indole
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • 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
  • CN1CCC2=C(CC1)NC3=C2C=CC(=C3)OC
Properties
C14H18N2O
Molar mass 230.311 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Tabernanthalog (TBG, DLX-007) [1] is a novel water-soluble, non-toxic azepinoindole [2] analog of the psychoactive drug Tabernanthine first synthesized by Professor David E. Olson at UC Davis.

Tabernanthalog is a non-hallucinogenic serotonin 5-HT2A receptor agonist. [3] It is also a serotonin 5-HT2B receptor antagonist. [3] The drug is described as having high selectivity for the serotonin 5-HT2 receptors. [3] Other targets of the drug include monoamine oxidase A (MAO-A), the α2A-adrenergic receptor, the serotonin 5-HT1B and 5-HT2C receptors, and the serotonin transporter (SERT). [3]

In rodents, it was found to promote structural neural plasticity, reduce drug seeking behavior, and produce antidepressant like effects. [1] [4] [5] [6] It has also been shown that it effectively reduces motivation for heroin and alcohol in rats. This indicates its efficacy in animals with a history of heroin and alcohol polydrug use. [6]

Due to the rapidly-induced and enduring neuroplasticity, tabernanthalog is a member of the class of compounds known as non-hallucinogenic psychoplastogens. [1] This compound, as well as related compounds, are licensed by Delix Therapeutics and are being developed as potential medicines for neuropsychiatric disorders. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Psychedelic drug</span> Hallucinogenic class of psychoactive drug

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states and a perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to psychedelia like salvia and MDMA, respectively.

<span class="mw-page-title-main">5-MeO-DMT</span> Chemical compound

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), also known as O-methylbufotenin or mebufotenin, is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by the glands of at least one toad species, the Colorado River toad. It may occur naturally in humans as well. Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Slang terms include five-methoxy, the power, bufo, and toad venom.

<span class="mw-page-title-main">Ibogaine</span> Psychoactive substance found in plants in the family Apocynaceae

Ibogaine is a psychoactive indole alkaloid obtained either by extraction from plants in the family Apocynaceae such as Tabernanthe iboga, Voacanga africana, and Tabernaemontana undulata or by semi-synthesis from the precursor compound voacangine, another plant alkaloid. The total synthesis of ibogaine was described in 1956. Structural elucidation by X-ray crystallography was completed in 1960.

5-HT<sub>2B</sub> receptor Mammalian protein found in Homo sapiens

5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, the 5-HT2B receptor is Gq/G11-protein coupled, leading to downstream activation of phospholipase C.

Iboga-type alkaloids are a set of monoterpene indole alkaloids comprising naturally occurring compounds found in Tabernanthe and Tabernaemontana, as well as synthetic structural analogs. Naturally occurring iboga-type alkaloids include ibogamine, ibogaine, tabernanthine, and other substituted ibogamines. Many iboga-type alkaloids display biological activities such as cardiac toxicity and psychoactive effects, and some have been studied as potential treatments for drug addiction.

<span class="mw-page-title-main">DLX-001</span> Chemical compound

DLX-001, also known as AAZ-A-154 or as (R)-5-methoxy-N,N-dimethyl-α-methylisotryptamine, is a novel isotryptamine derivative which acts as a serotonin 5-HT2A receptor agonist discovered and synthesized by the lab of Professor David E. Olson at the University of California, Davis. It is being developed for the treatment of major depressive disorder and other central nervous system disorders.

Psychoplastogens are a group of small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single administration. Several existing psychoplastogens have been identified and their therapeutic effects demonstrated; several are presently at various stages of development as medications including ketamine, MDMA, scopolamine, and the serotonergic psychedelics, including LSD, psilocin, DMT, and 5-MeO-DMT. Compounds of this sort are being explored as therapeutics for a variety of brain disorders including depression, addiction, and PTSD. The ability to rapidly promote neuronal changes via mechanisms of neuroplasticity was recently discovered as the common therapeutic activity and mechanism of action.

David E. Olson is an American chemist and neuroscientist. He is an associate professor of chemistry, biochemistry and molecular medicine at the University of California, Davis, and is the founding director of the UC Davis Institute for Psychedelics and Neurotherapeutics.

<span class="mw-page-title-main">Delix Therapeutics</span> American biotech company

Delix Therapeutics is an American biotech company based in Boston, Massachusetts. The company develops novel neuroplasticity-promoting therapeutics for central nervous system (CNS) diseases such as depression and post-traumatic stress disorder (PTSD). It was co-founded in 2019 by David E. Olson and Nick Haft.

<span class="mw-page-title-main">6-Fluoro-DET</span> Chemical compound

6-Fluoro-DET is a substituted tryptamine derivative related to drugs such as DET and 5-fluoro-DET. It acts as a partial agonist at the 5-HT2A receptor, but while it produces similar physiological effects to psychedelic drugs, it does not appear to produce psychedelic effects itself even at high doses. For this reason it saw some use as an active placebo in early clinical trials of psychedelic drugs but was regarded as having little use otherwise, though more recent research into compounds such as AL-34662, TBG and AAZ-A-154 has shown that these kind of non-psychedelic 5-HT2A agonists can have various useful applications.

<span class="mw-page-title-main">ITI-1549</span> Non-hallucinogenic 5-HT2A agonist

ITI-1549 is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist which is under development for the treatment of mood disorders and other psychiatric disorders. In addition to acting at the serotonin 5-HT2A receptor, it is also an antagonist of the serotonin 5-HT2B receptor and an agonist of the serotonin 5-HT2C receptor. The drug's route of administration has not been specified.

<span class="mw-page-title-main">6-MeO-DMT</span> Non-hallucinogenic 5-HT2A agonist

6-MeO-DMT, or 6-methoxy-N,N-dimethyltryptamine, also known as 6-OMe-DMT, is a serotonergic drug of the tryptamine family. It is the 6-methoxy derivative of the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and is a positional isomer of the serotonergic psychedelic 5-MeO-DMT.

<span class="mw-page-title-main">Isotryptamine</span> Chemical compound

Isotryptamine, also known as 2-(1-indolyl)ethylamine, is a chemical compound and positional isomer of tryptamine.

<span class="mw-page-title-main">6-MeO-isoDMT</span> Serotonergic psychoplastogen

6-MeO-isoDMT, or 6-OMe-isoDMT, also known as 6-methoxy-N,N-dimethylisotryptamine, is a serotonin 5-HT2A receptor agonist, putative serotonergic psychedelic, and psychoplastogen of the isotryptamine group. It is the isotryptamine analogue of the psychedelic 5-MeO-DMT and is a positional isomer of the non-hallucinogenic psychoplastogen 5-MeO-isoDMT.

<span class="mw-page-title-main">5-MeO-isoDMT</span> Serotonergic psychoplastogen

5-MeO-isoDMT, or 5-OMe-isoDMT, also known as 5-methoxy-N,N-dimethylisotryptamine, is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist and psychoplastogen of the isotryptamine group. It is the isotryptamine analogue of the non-hallucinogenic 6-MeO-DMT and is a positional isomer of the psychedelic 6-MeO-isoDMT.

isoDMT Serotonergic drug

isoDMT, also known as N,N-dimethylisotryptamine, is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist and psychoplastogen of the isotryptamine group. It is the isotryptamine homologue of dimethyltryptamine (DMT), a more well-known serotonergic psychedelic of the tryptamine family, and represents a small structural modification of DMT.

<span class="mw-page-title-main">Ibogainalog</span> Serotonergic psychedelic

Ibogainalog (IBG), also known as 9-methoxyibogaminalog, is a serotonergic psychedelic and psychoplastogen related to ibogaine but with a simplified chemical structure.

DLX-159 is a putatively non-hallucinogenic psychoplastogen which is under development for the treatment of major depressive disorder and other psychiatric disorders. It is taken by mouth.

References

  1. 1 2 3 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.
  2. Hester JB, Tang AH, Keasling HH, Veldkamp W (January 1968). "Azepinoindoles. I. Hexahydroazepino[4,5-b]indoles". Journal of Medicinal Chemistry. 11 (1): 101–106. doi:10.1021/jm00307a023. PMID   5637151.
  3. 1 2 3 4 Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, Vargas MV, McCarroll MN, Taylor JC, Myers-Turnbull D, Liu T, Yaghoobi B, Laskowski LJ, Anderson EI, Zhang G, Viswanathan J, Brown BM, Tjia M, Dunlap LE, Rabow ZT, Fiehn O, Wulff H, McCorvy JD, Lein PJ, Kokel D, Ron D, Peters J, Zuo Y, Olson DE (January 2021). "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature. 589 (7842): 474–479. doi:10.1038/s41586-020-3008-z. PMC   7874389 . PMID   33299186.
  4. 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.
  5. 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.
  6. 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.
  7. Grace B (6 March 2021). "Can we take the high out of psychedelics?". Wired. Retrieved 12 July 2022.