Ibogainalog

Ibogainalog

Clinical data
Other names	IBG; 9-Methoxyibogaminalog; 9-MeO-ibogaminalog
Drug class	Serotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen; Psychoplastogen
Identifiers
IUPAC name 9-methoxy-3-methyl-2,4,5,6-tetrahydro-1H-azepino[4,5-b]indole
CAS Number	802581-10-8
PubChem CID	370423
ChemSpider	328813
ChEMBL	ChEMBL2009371
Chemical and physical data
Formula	C14H18N2O
Molar mass	230.311 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN1CCC2=C(CC1)NC3=C2C=C(C=C3)OC
InChI InChI=1S/C14H18N2O/c1-16-7-5-11-12-9-10(17-2)3-4-13(12)15-14(11)6-8-16/h3-4,9,15H,5-8H2,1-2H3 Key:RVVJOBLZASPMDJ-UHFFFAOYSA-N

Ibogainalog (IBG), also known as 9-methoxyibogaminalog, is a serotonergic psychedelic and psychoplastogen related to ibogaine but with a simplified chemical structure. ^{[1] [2] [3]}

Pharmacology

It acts as a serotonin 5-HT_2A receptor agonist, serotonin 5-HT_2B receptor antagonist, and also interacts with other serotonin receptors, such as the serotonin 5-HT_1F receptor (agonist), 5-HT_2C receptor (very weak partial agonist or antagonist), and 5-HT₆ receptor (agonist). ^{[3] [4]} Unlike noribogaine, IBG shows no activation of the opioid receptors or κ-opioid receptor agonism. ^[3] In addition to its actions at serotonin receptors, IBG inhibits certain nicotinic acetylcholine receptors. ^[5]

The drug produces the head-twitch response in animals and hence shows psychedelic-like effects. ^{[1] [3]} However, it has reduced hallucinogen-like effects compared to 5-MeO-DMT. ^[1] Conversely, tabernanthalog (TBG), a simplified analogue of tabernanthine and positional isomer of IBG, appears to be completely non-hallucinogenic. ^{[1] [3]} IBG shows comparable psychoplastogenic activity to ibogaine. ^[1] In contrast to ibogaine, IBG and TBG appear to have much less or no potential for cardiotoxicity secondary to hERG inhibition. ^{[1] [3]} However, TBG showed a better overall safety profile than IBG and was selected for development instead of IBG. ^{[1] [3]} IBG shows analgesic effects against neuropathic pain and visceral pain in animals that appear to be mediated by serotonin 5-HT_2A receptor activation. ^[4]

Chemistry

IBG can be viewed as a conformationally restricted analogue of 5-MeO-DMT, whereas TBG can be viewed as a conformationally restricted analogue of 6-MeO-DMT. ^{[2] [3]} Owing to their simplified structures, the chemical syntheses of IBG and TBG are much more practical than the synthesis of ibogaine. ^[1]

See also

• Ibogaminalog (DM-506)

References

1. Zięba A, Stępnicki P, Matosiuk D, Kaczor AA (December 2021). "Overcoming Depression with 5-HT_2A Receptor Ligands". International Journal of Molecular Sciences. 23 (1): 10. doi: 10.3390/ijms23010010 . PMC   8744644 . PMID   35008436.
2. Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT_2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID   38033123.
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. doi:10.1038/s41586-020-3008-z. PMC   7874389 . PMID   33299186.
4. Arias HR, Micheli L, Rudin D, Bento O, Borsdorf S, Ciampi C, et al. (August 2024). "Non-hallucinogenic compounds derived from iboga alkaloids alleviate neuropathic and visceral pain in mice through a mechanism involving 5-HT_2A receptor activation". Biomedicine & Pharmacotherapy. 177: 116867. doi:10.1016/j.biopha.2024.116867. hdl: 2158/1371514 . PMID   38889634.
5. Tae HS, Ortells MO, Yousuf A, Xu SQ, Akk G, Adams DJ, et al. (May 2024). "Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABA_A receptor and Ca_V2.2 channel". Biochemical Pharmacology. 223: 116183. doi:10.1016/j.bcp.2024.116183. PMC  11151864. PMID   38580167.