TACT908

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| class = Serotonin receptor agonist; Serotonin 5-HT_1B receptor agonist; Non-hallucinogenic serotonin 5-HT_2A receptor agonist

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| PubChem = 169203122

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| synonyms = TACT-908; Compound 28-12; 2ZEDMA; [2-(Indolizin-1-yl)ethyl]dimethylamine; Indolizine-DMT

| IUPAC_name = 2-indolizin-1-yl-N,N-dimethylethanamine

| C=12 | H=16 | N=2

| SMILES = CN(C)CCC1=C2C=CC=CN2C=C1

| StdInChI = 1S/C12H16N2/c1-13(2)9-6-11-7-10-14-8-4-3-5-12(11)14/h3-5,7-8,10H,6,9H2,1-2H3

| StdInChIKey = CBZZXMYTGARRHB-UHFFFAOYSA-N

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TACT908, also known as [2-(indolizin-1-yl)ethyl]dimethylamine (2ZEDMA), is a serotonin receptor agonist which is under development for the treatment of cluster headaches.{{cite patent | country=WO | number=2023183613A2 | inventor=Matthew J. Baggott | status=patent | title=Indolizine compounds for the treatment of mental disorders or inflammation | pubdate=2023 September 28 | gdate= | fdate=24 March 2023 | pridate=24 March 2023 | assign1=Tactogen | url=https://patents.google.com/patent/WO2023183613A2/ | quote=Compound 28-12 oxalate showed relatively few interactions with other potential binding sites, with agonism of 5-HT1B receptors (EC50 of approximately 143.32 nM) being the only interaction with sub-micromolar potency. [...] Compound 28-12 oxalate ([2-(indolizin-1-yl)ethyl]dimethylamine oxalate) was evaluated for activity at 47 target sites at ten concentrations up to 30 μM, with EC50 or IC0 determined whenever possible. [...] Surprisingly, compound 28-12 oxalate showed high potency and partial agonist effects at 5-HT2AR. The EC50 was estimated as approximately 52.25 nM, while the maximum effect was approximately 30% of the response produced by 5-HT (Figure 4). These partial agonist effects suggest the unexpected use of compound 28-12 oxalate and other indolizine derivatives as modulators of 5-HT2AR activity in situations where hallucinatory effects would be undesirable. [...] Compound 28-12 oxalate showed relatively few interactions with other potential binding sites, with agonism of 5-HT1B receptors (EC50 of approximately 143.32 nM) being the only interaction with sub-micromolar potency. This further supports the use of compound 28-12 oxalate and other compounds of Formula I for conditions that include signs or symptoms related to headache, inflammation, stress sensitivity, addiction and reward system dysfunction, mood, anxiety, and aggression. }}{{cite web | vauthors = Haichin M | title=Psychedelics Drug Development Tracker | website=Psychedelic Alpha | url=https://psychedelicalpha.com/data/psychedelic-drug-development-tracker | date=2024 | access-date=29 January 2025}}{{cite web | title=Tactogen Inc – Pipeline | website=Tactogen Inc | date=8 February 2021 | publisher=Tactogen | url=https://tactogen.com/pipeline/ | access-date=29 January 2025 | quote=OUR PIPELINE: [...] COMPOUND: TACT908. TARGETS: 5-HT1B, 5-HT2A ***. INDICATION: Cluster Headache. Prevalence: 0.24%. STATUS: Preclinical. [...] ***Partial agonist at 2A, non-hallucinogenic. }} It is an positional isomer of the famous tryptamine serotonergic psychedelic N,N-dimethyltryptamine (DMT) in which the indole ring has been replaced with an indolizine ring.

The drug acts as a serotonin 5-HT_1B and 5-HT_2A receptor agonist. Its {{Abbrlink|EC₅₀|half-maximal effective concentration}} at the serotonin 5-HT_2A receptor is 52{{nbsp}}nM ({{Abbrlink|E_max|maximal efficacy}} ≈ 30% of that of serotonin) and its {{Abbr|EC₅₀|half-maximal effective concentration}} at the serotonin 5-HT_1B receptor is 143{{nbsp}}nM. TACT908 is said to be a non-hallucinogenic serotonin 5-HT_2A receptor agonist. It showed little or no activity at 45{{nbsp}}other screened targets, including the serotonin 5-HT_1A, 5-HT_2B, and 5-HT₃ receptors as well as the monoamine transporters (MATs). Other serotonin receptors besides the preceding, such as the serotonin 5-HT_2C receptor, were not assessed. The drug was a weak monoamine oxidase inhibitor (MAOI), specifically of monoamine oxidase A (MAO-A) ({{Abbrlink|IC₅₀|half-maximal inhibitory concentration}} = 7,252{{nbsp}}nM).

TACT908 is under development by Tactogen. It was patented by Matthew Baggott of Tactogen in 2023. As of January 2025, the drug is in preclinical research for cluster headaches.

The α-methyl and N-desmethyl analogue of TACT908, 1ZP2MA ([1-(indolizin-1-yl)propan-2-yl](methyl)amine or 1-(indolizin-1-yl)-N-methylpropan-2-amine), has also been characterized and described. It is the indolizine analogue of α,N-dimethyltryptamine (α,N-DMT or N-methyl-{{abbr|αMT|α-methyltryptamine}}). 1ZP2MA was found to be a potent dopamine releasing agent, with an {{Abbr|EC₅₀|half-maximal effective concentration}} of 62{{nbsp}}nM.