Ibogaminalog

Ibogaminalog
Clinical data
Other names	DM-506; DM506
Drug class	Non-selective serotonin receptor modulator; Non-hallucinogenic serotonin 5-HT2A receptor partial agonist
Identifiers
	IUPAC name 3-methyl-2,4,5,6-tetrahydro-1H-azepino[4,5-b]indole;
CAS Number	7546-66-9 ;
PubChem CID	24183;
ChemSpider	22605;
CompTox Dashboard (EPA)	DTXSID70226391 ;
Chemical and physical data
Formula	C13H16N2
Molar mass	200.285 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1CCC2=C(CC1)NC3=CC=CC=C23;
	InChI InChI=1S/C13H16N2/c1-15-8-6-11-10-4-2-3-5-12(10)14-13(11)7-9-15/h2-5,14H,6-9H2,1H3; Key:WBCPONKOWIDTJM-UHFFFAOYSA-N;

Ibogaminalog (developmental code name DM-506) is a non-selective and non-psychedelic serotonin receptor modulator of the ibogalog group related to the iboga alkaloid ibogamine but with a simplified chemical structure. It was first described in the 1960s but was subsequently further studied and reported on in the 2020s.^[1]^[2]^[3]^[4]^[5]^[6]

Pharmacology

Ibogaminalog is known to act as an agonist of serotonin receptors, including of the serotonin 5-HT_2A receptor (K_i = 17–11,190 nM; EC₅₀Tooltip half-maximal effective concentration = 2.9–34 nM; E_maxTooltip maximal efficacy = 33–76%), the serotonin 5-HT_2B receptor (K_i = 16.5–63,780 nM; EC₅₀ = 2.9–33 nM; E_max = 68–69%), and the serotonin 5-HT₆ receptor (EC₅₀ = 2.9 nM; E_max = 96%), and as an inverse agonist of the serotonin 5-HT₇ receptor (I_maxTooltip maximal inhibition = 14%).^[4]^[3]^[7]^[8]

It is a weak to very weak monoamine reuptake inhibitor, including of serotonin, norepinephrine, and dopamine (IC₅₀Tooltip half-maximal inhibitory concentration = 3,100 nM, 9,500 nM, and 70,000 nM, respectively), whereas it is not a significant monoamine oxidase inhibitor (MAOI) of MAO-A or MAO-B.^[7] The drug also acts weakly as a negative allosteric modulator of the α₇ and α₉α₁₀ nicotinic acetylcholine receptors.^[2]

Ibogaminalog does not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and hence may be non-hallucinogenic in humans.^[4] On the other hand, it has been found to produce sedative, antidepressant-like, anxiolytic-like, antiaddictive-like, and analgesic-like effects in rodents.^[4]^[7]^[5]^[3]

References

^ US 3529062, Renner U, "Indole derivatives as antitussive agents.", issued 15 September 1970, assigned to Novartis Corp.
^ ^a ^b 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 GABA_A receptor and Ca_V2.2 channel". Biochemical Pharmacology. 223: 116183. doi:10.1016/j.bcp.2024.116183. PMC 11151864. PMID 38580167.{{cite journal}}: CS1 maint: article number as page number (link)
^ ^a ^b ^c Arias HR, Micheli L, Rudin D, Bento O, Borsdorf S, Ciampi C, et al. (June 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.{{cite journal}}: CS1 maint: article number as page number (link)
^ ^a ^b ^c ^d Arias HR, Rudin D, Hines DJ, Contreras A, Gulsevin A, Manetti D, et al. (March 2024). "The novel non-hallucinogenic compound DM506 (3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole) induces sedative- and anxiolytic-like activity in mice by a mechanism involving 5-HT_2A receptor activation". European Journal of Pharmacology. 966: 176329. doi:10.1016/j.ejphar.2024.176329. hdl:2158/1354752. PMID 38253116.{{cite journal}}: CS1 maint: article number as page number (link)
^ ^a ^b Looschen K, Khatri SN, Maulik M, Salisbury C, Carman AF, Corriveau K, et al. (June 2024). "Novel psychoplastogen DM506 reduces cue-induced heroin-seeking and inhibits tonic GABA currents in the Prelimbic Cortex". Neurochemistry International. 178: 105785. doi:10.1016/j.neuint.2024.105785. hdl:2158/1371513. PMID 38838988.{{cite journal}}: CS1 maint: article number as page number (link)
^ Tae HS, Ortells MO, Tekarli BJ, Manetti D, Romanelli MN, McIntosh JM, et al. (July 2023). "DM506 (3-Methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole fumarate), a Novel Derivative of Ibogamine, Inhibits α7 and α9α10 Nicotinic Acetylcholine Receptors by Different Allosteric Mechanisms". ACS Chemical Neuroscience. 14 (14): 2537–2547. doi:10.1021/acschemneuro.3c00212. PMID 37386821.
^ ^a ^b ^c 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.{{cite journal}}: CS1 maint: article number as page number (link)
^ 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. hdl:2158/1423286. PMID 39938347.{{cite journal}}: CS1 maint: article number as page number (link)

[US3529062-1] US 3529062, Renner U, "Indole derivatives as antitussive agents.", issued 15 September 1970, assigned to Novartis Corp.

[TaeOrtellsYousuf2024-2] 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 GABA_A receptor and Ca_V2.2 channel". Biochemical Pharmacology. 223: 116183. doi:10.1016/j.bcp.2024.116183. PMC 11151864. PMID 38580167.{{cite journal}}: CS1 maint: article number as page number (link)

[AriasMicheliRudin2024-3] Arias HR, Micheli L, Rudin D, Bento O, Borsdorf S, Ciampi C, et al. (June 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.{{cite journal}}: CS1 maint: article number as page number (link)

[AriasRudinHines2024-4] Arias HR, Rudin D, Hines DJ, Contreras A, Gulsevin A, Manetti D, et al. (March 2024). "The novel non-hallucinogenic compound DM506 (3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole) induces sedative- and anxiolytic-like activity in mice by a mechanism involving 5-HT_2A receptor activation". European Journal of Pharmacology. 966: 176329. doi:10.1016/j.ejphar.2024.176329. hdl:2158/1354752. PMID 38253116.{{cite journal}}: CS1 maint: article number as page number (link)

[LooschenKhatriMaulik2024-5] Looschen K, Khatri SN, Maulik M, Salisbury C, Carman AF, Corriveau K, et al. (June 2024). "Novel psychoplastogen DM506 reduces cue-induced heroin-seeking and inhibits tonic GABA currents in the Prelimbic Cortex". Neurochemistry International. 178: 105785. doi:10.1016/j.neuint.2024.105785. hdl:2158/1371513. PMID 38838988.{{cite journal}}: CS1 maint: article number as page number (link)

[6] Tae HS, Ortells MO, Tekarli BJ, Manetti D, Romanelli MN, McIntosh JM, et al. (July 2023). "DM506 (3-Methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole fumarate), a Novel Derivative of Ibogamine, Inhibits α7 and α9α10 Nicotinic Acetylcholine Receptors by Different Allosteric Mechanisms". ACS Chemical Neuroscience. 14 (14): 2537–2547. doi:10.1021/acschemneuro.3c00212. PMID 37386821.

[AriasRudinLuethi2025-7] 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.{{cite journal}}: CS1 maint: article number as page number (link)

[AriasMicheliJensen2025-8] 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. hdl:2158/1423286. PMID 39938347.{{cite journal}}: CS1 maint: article number as page number (link)

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Ibogaminalog

Pharmacology

See also

References

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