TACT908

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. 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 EC₅₀Tooltip half-maximal effective concentration at the serotonin 5-HT_2A receptor is 52 nM (E_maxTooltip maximal efficacy ≈ 30% of that of serotonin) and its EC₅₀ at the serotonin 5-HT_1B receptor is 143 nM. TACT908 is said to be a non-hallucinogenic serotonin 5-HT_2A receptor agonist. It showed little or no activity at 45 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) (IC₅₀Tooltip half-maximal inhibitory concentration = 7,252 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-αMT). 1ZP2MA was found to be a potent dopamine releasing agent, with an EC₅₀ of 62 nM.