1Z2MAP1O

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| class = Monoamine releasing agent; Serotonin 5-HT_1B receptor agonist; Serotonin 5-HT_2B receptor antagonist; Entactogen

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| CAS_number = 2110204-31-2

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| PubChem = 165756415

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| ChemSpiderID = 26962386

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| synonyms = 1-(Indolizin-3-yl)-2-(methylamino)propan-1-one; Structure XLX

| IUPAC_name = 1-indolizin-3-yl-2-(methylamino)propan-1-one

| C=12 | H=14 | N=2 | O=1

| SMILES = CC(C(=O)C1=CC=C2N1C=CC=C2)NC

| StdInChI = 1S/C12H14N2O/c1-9(13-2)12(15)11-7-6-10-5-3-4-8-14(10)11/h3-9,13H,1-2H3

| StdInChIKey = BFSFBVDVCJVAMW-UHFFFAOYSA-N

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1Z2MAP1O, also known as 1-(indolizin-3-yl)-2-(methylamino)propan-1-one, is a monoamine releasing agent and serotonin receptor modulator of the indolizine class.{{ cite patent | country=WO | number=2023081306A1 | inventor=Baggott MJ | status=application | title=Indolizine compounds for the treatment of mental disorders or mental enhancement | pubdate=11 May 2023 | gdate= | fdate=3 November 2022 | pridate=3 November 2022 | assign1=Tactogen | url=https://patents.google.com/patent/WO2023081306A1/ | quote=FIG. 1 depicts response curves for 1-(indolizin-3-yl)-2-(methylamino)propan-1-one (Structure XLX) in a serotonin (SERT) release assay and a dopamine (DAT) release assay. [...] EXAMPLE 11: In vitro activity assessments 1-(indolizin-3-yl)-2-(methylamino)propan-1-one (Structure XLX) was evaluated for activity at 47 target sites at ten concentrations up to 30 μM, with EC50 or IC50 determined whenever possible. Activity was detected only at 5-HT1B (agonist effects with an EC50 of 1.13 μM) and 5-HT2B (antagonist effects with an IC50 of 2.14 μM) receptors and at DAT (IC50 of 2.41 μM) and NET (IC50 of 5.69 μM). [...] EXAMPLE 12: Human Monoamine Transporter (hMAT) Release Assays [...] To assess the effects of indolizine derivatives on extracellular dopamine and serotonin concentrations, in vitro measures of serotonin and dopamine release were made using Chinese hamster ovary cells that stably expressed human monoamine transporters, dopamine (hDAT) and serotonin (hSERT) transporter. Dextroamphetamine and norfenfluramine were used as reference releasers of dopamine and serotonin, respectively. [...] Assay results revealed that 1-(indolizin-3-yl)-2-(methylamino)propan-1-one was more potent at releasing DAT than 5-HT, with a DAT/SERT ratio suggesting MDMA-like effects. [...] Table 4: Effects of Structure XLX on neurotransmitter release from DAT and SERT: 1-(indolizin-3-yl)-2-(methylamino)propan-1-one: EC50 DAT (nM): 227. EC50 SERT (nM): 109. DAT/SERT ratio*: 2.1. *DAT/SERT ratios are calculated here as (DAT EC50) * /(SERT EC50) * where larger numbers indicate higher DAT selectivity hSERT release measurement methods. }} It is an analogue of BK-NM-AMT (β-keto-N-methyl-α-methyltryptamine) in which the indole ring has been replaced with an indolizine ring.

1Z2MAP1O has been found to be a serotonin and dopamine releasing agent as well as a weak serotonin 5-HT_1B receptor agonist and serotonin 5-HT_2B receptor antagonist. Conversely, its activity as a norepinephrine releasing agent was not reported, and it was inactive at the remaining sites of the 47{{nbsp}}screened targets. The drug's {{Abbrlink|EC₅₀|half-maximal effective concentration}} values for induction of monoamine release were 109{{nbsp}}nM for serotonin and 227{{nbsp}}nM for dopamine in Chinese hamster ovary (CHO) cells expressing the human monoamine transporters (MATs). The dopamine/serotonin ratio was 0.48. Its {{Abbr|EC₅₀|half-maximal effective concentration}} at the serotonin 5-HT_1B receptor was 1,130{{nbsp}}nM, whereas its {{Abbrlink|IC₅₀|half-maximal inhibitory concentration}} values were 2,140{{nbsp}}nM at the serotonin 5-HT_2B receptor, 2,410{{nbsp}}nM at the dopamine transporter (DAT), and 5,690{{nbsp}}nM at the norepinephrine transporter (NET). 1Z2MAP1O's inhibition of the serotonin transporter (SERT) was not reported.

1Z2MAP1O was patented by Matthew Baggott of Tactogen in 2023.