DFMDA

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 451607745

| IUPAC_name = 1-(2,2-Difluoro-1,3-benzodioxol-5-yl)propan-2-amine

| image = DFMDA.svg

| image_class = skin-invert-image

| tradename =

| pregnancy_category =

| legal_CA = Schedule I

| legal_DE = NpSG

| legal_UK = Class A

| legal_status =

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 910393-51-0

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 8Q2ANL037S

| ATC_prefix = none

| ATC_suffix =

| ChemSpiderID = 26495356

| PubChem = 57467735

| SMILES = CC(Cc1ccc2c(c1)OC(O2)(F)F)N

| StdInChI = 1S/C10H11F2NO2/c1-6(13)4-7-2-3-8-9(5-7)15-10(11,12)14-8/h2-3,5-6H,4,13H2,1H3

| StdInChIKey = BHDXKBALNFHXDV-UHFFFAOYSA-N

| C=10 | H=11 | F=2 | N=1 | O=2

}}

Difluoromethylenedioxyamphetamine (DFMDA, DiFMDA) is a substituted derivative of 3,4-methylenedioxyamphetamine (MDA), which was developed by Daniel Trachsel and coworkers, along with the corresponding fluorinated derivatives of MDMA, MDEA, BDB and MBDB, with the aim of finding a non-neurotoxic drug able to be used as a less harmful substitute for entactogenic drugs such as MDMA. Since a major route of the normal metabolism of these compounds is scission of the methylenedioxy ring, producing neurotoxic metabolites such as alpha-methyldopamine, it was hoped that the difluoromethylenedioxy bioisostere would show increased metabolic stability and less toxicity.{{cite journal |vauthors=Trachsel D, Hadorn M, Baumberger F |title=Synthesis of fluoro analogues of 3,4-(methylenedioxy)amphetamine (MDA) and its derivatives |journal=Chemistry & Biodiversity |volume=3 |issue=3 |pages=326–36 |date=March 2006 |pmid=17193269 |doi=10.1002/cbdv.200690035 |citeseerx=10.1.1.688.5803 |s2cid=23036634 }}{{cite journal | vauthors = Meanwell NA |title=Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design |journal=Journal of Medicinal Chemistry |volume= 54|issue= 8|pages= 2529–91|date=March 2011 |pmid=21413808 |doi=10.1021/jm1013693 }}{{cite journal | vauthors = Takač MJ, Magina JD, Takač T | title = Evaluation of phenylethylamine type entactogens and their metabolites relevant to ecotoxicology - a QSAR study | journal = Acta Pharmaceutica | location = Zagreb, Croatia | volume = 69 | issue = 4 | pages = 563–584 | date = December 2019 | pmid = 31639096 | doi = 10.2478/acph-2019-0038 | s2cid = 204850967 | doi-access = free }}

These compounds have not yet been tested in animals to verify whether they show similar pharmacological activity to the non-fluorinated parent compounds, although in vitro binding studies show DFMDA to have a SERT affinity in between that of MDA and MDMA.{{cite journal |vauthors=Walline CC, Nichols DE, Carroll FI, Barker EL |title=Comparative molecular field analysis using selectivity fields reveals residues in the third transmembrane helix of the serotonin transporter associated with substrate and antagonist recognition |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=325 |issue=3 |pages=791–800 |date=June 2008 |pmid=18354055 |pmc=2637348 |doi=10.1124/jpet.108.136200 }} It is also now generally accepted that MDMA neurotoxicity results from a variety of different causes and is not solely due to accumulation of alpha-methyldopamine,{{cite journal |vauthors=Capela JP, Carmo H, Remião F, Bastos ML, Meisel A, Carvalho F |title=Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview |journal=Molecular Neurobiology |volume=39 |issue=3 |pages=210–71 |date=June 2009 |pmid=19373443 |doi=10.1007/s12035-009-8064-1 |citeseerx=10.1.1.670.6897 |s2cid=21190104 }}{{cite journal |vauthors=Sarkar S, Schmued L |title=Neurotoxicity of ecstasy (MDMA): an overview |journal=Current Pharmaceutical Biotechnology |volume=11 |issue=5 |pages=460–9 |date=August 2010 |pmid=20420572 |doi= 10.2174/138920110791591490}}{{cite journal |vauthors=Escubedo E, Abad S, Torres I, Camarasa J, Pubill D |title=Comparative neurochemical profile of 3,4-methylenedioxymethamphetamine and its metabolite alpha-methyldopamine on key targets of MDMA neurotoxicity |journal=Neurochemistry International |volume=58 |issue=1 |pages=92–101 |date=January 2011 |pmid=21074589 |doi=10.1016/j.neuint.2010.11.001 |s2cid=2853533 }} making it unclear how much less neurotoxic DFMDA and related drugs would be in practice.