Chemistry:TACT908

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TACT908, also known as [2-(indolizin-1-yl)ethyl]dimethylamine (2ZEDMA), is a serotonin receptor agonist of the indolizinylethylamine family which is under development for the treatment of cluster headaches.[1][2][3] It is a positional isomer of the tryptamine serotonergic psychedelic N,N-dimethyltryptamine (DMT) in which the indole ring has been replaced with an indolizine ring.[1]

The drug acts as a serotonin 5-HT1B and 5-HT2A receptor agonist.[1][3] Its EC50 at the serotonin 5-HT2A receptor is 52 nM (Emax ≈ 30% of that of serotonin) and its EC50 at the serotonin 5-HT1B receptor is 143 nM.[1] TACT908 is said to be a non-hallucinogenic serotonin 5-HT2A receptor agonist.[1][3] It showed little or no activity at 45 other screened targets, including the serotonin 5-HT1A, 5-HT2B, and 5-HT3 receptors as well as the monoamine transporters (MATs).[1] Other serotonin receptors besides the preceding, such as the serotonin 5-HT2C receptor, were not assessed.[1] The drug was a weak monoamine oxidase inhibitor (MAOI), specifically of monoamine oxidase A (MAO-A) (IC50 = 7,252 nM).[1]

TACT908 is under development by Tactogen.[1][2][3] It was patented by Matthew Baggott of Tactogen in 2023.[1] As of January 2025, the drug is in preclinical research for cluster headaches.[2][3]

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.[1] It is the indolizine analogue of α,N-dimethyltryptamine (α,N-DMT or N-methyl-αMT).[1] 1ZP2MA was found to be a potent dopamine releasing agent, with an EC50 of 62 nM.[1]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 Matthew J. Baggott, "Indolizine compounds for the treatment of mental disorders or inflammation", WO patent 2023183613A2, published 2023 September 28, assigned to Tactogen
  2. ↑ 2.0 2.1 2.2 "Psychedelics Drug Development Tracker". 2024. https://psychedelicalpha.com/data/psychedelic-drug-development-tracker. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "Tactogen Inc – Pipeline". Tactogen. 8 February 2021. https://tactogen.com/pipeline/. "OUR PIPELINE: [...] COMPOUND: TACT908. TARGETS: 5-HT1B, 5-HT2A ***. INDICATION: Cluster Headache. Prevalence: 0.24%. STATUS: Preclinical. [...] ***Partial agonist at 2A, non-hallucinogenic."