Difluoromethylenedioxyamphetamine (DiFMDA) is a modified derivative of 3,4-methylenedioxyamphetamine (MDA), a compound initially developed by Daniel Trachsel and colleagues. This development also included the creation of fluorinated variants of MDMA, MDEA, BDB, and MBDB. The primary objective was to identify a non-neurotoxic substance that could serve as a safer alternative to entactogenic drugs like MDMA.
The rationale behind these modifications stemmed from the understanding that one of the major metabolic pathways for these compounds involves the cleavage of the methylenedioxy ring, producing neurotoxic byproducts such as alpha-methyldopamine. It was hypothesized that by substituting the methylenedioxy group with a difluoromethylenedioxy bioisostere, the resulting compound would exhibit enhanced metabolic stability and reduced toxicity.
To date, these compounds have not undergone animal testing to confirm their pharmacological effects compared to the non-fluorinated parent compounds. However, in vitro binding studies indicate that DiFMDA possesses serotonin transporter (SERT) affinity levels falling between those of MDA and MDMA.
It is important to note that contemporary scientific consensus acknowledges that MDMA’s neurotoxicity is a complex outcome with multiple contributing factors rather than being solely attributed to the accumulation of alpha-methyldopamine. This complexity leaves uncertainties regarding the actual extent of reduced neurotoxicity that DiFMDA and related compounds might offer in practical terms.

IUPAC name
CAS Number910393-51-0 
PubChem CID57467735
CompTox Dashboard (EPA)DTXSID10726729
Chemical and physical data
Molar mass215.200 g·mol−1


  • What is DiFMDA?
  • DiFMDA, or Difluoromethylenedioxyamphetamine, is a chemical compound derived from 3,4-methylenedioxyamphetamine (MDA) and is part of a group of modified substances.
  • Why was DiFMDA developed?
  • DiFMDA was created, along with other fluorinated derivatives of certain entactogenic drugs, to explore the possibility of developing a non-neurotoxic alternative to substances like MDMA. The aim was to reduce potential neurotoxicity and enhance the safety profile of these compounds.
  • What is the purpose of using fluorination in drug development?
  • The introduction of fluorine atoms in drug development is often used to modify the chemical structure of compounds. In the case of DiFMDA, it was done to enhance metabolic stability and potentially reduce toxicity, especially neurotoxicity.
  • Has DiFMDA been tested in animals to determine its effects?
  • As of now, DiFMDA and related compounds have not undergone animal testing to confirm their pharmacological properties and potential effects. Research is ongoing to assess their properties.
  • What is known about DiFMDA’s serotonin transporter affinity?
  • In vitro binding studies suggest that DiFMDA exhibits serotonin transporter (SERT) affinity that falls between that of MDA and MDMA. However, this information is based on laboratory studies and requires further investigation.
  • Is DiFMDA considered a safer alternative to MDMA?
  • The concept of using DiFMDA and related compounds as safer alternatives to MDMA is based on the premise of reduced neurotoxicity. However, it is essential to note that the exact causes of MDMA’s neurotoxicity are complex and multifaceted. This complexity makes it unclear how much less neurotoxic DiFMDA and similar substances would be in practical use.
  • Is DiFMDA legal and available for recreational use?
  • The legal status of DiFMDA can vary by jurisdiction, and it may not be intended for recreational use. It is essential to research and comply with the laws and regulations in your specific location.
  • Are there potential health risks associated with DiFMDA use?
  • Since DiFMDA and related compounds are not extensively studied, the potential health risks remain uncertain. Any use of such substances should be approached with caution and under the guidance of healthcare professionals if deemed necessary.
  • Is DiFMDA widely available for purchase or use?
  • The availability of DiFMDA can vary widely, and it may not be readily accessible. Purchasing or using any chemical substance for recreational or research purposes should be done with extreme caution and full consideration of its legal status.
  • Where can I find more information about DiFMDA and its status in my region?
  • To learn more about DiFMDA and its legal status in your area, consult your local drug enforcement agencies or government websites focused on drug regulations and policies. Staying informed and responsible is crucial when dealing with such substances.


  1. Trachsel D, Hadorn M, Baumberger F (March 2006). “Development of fluoro analogs of 3,4-(methylenedioxy)amphetamine (MDA) and its derivatives.” This research focused on the synthesis of fluorinated variants of MDA and its analogs. The aim was to explore their potential applications in drug design. [Reference: Chemistry & Biodiversity, 3(3), 326–36]
  2. Meanwell NA (March 2011). “Recent Tactical Applications of Bioisosteres in Drug Design.” This article provides a synopsis of the practical use of bioisosteres in drug design. Bioisosteres are essential tools in modifying chemical structures for pharmacological purposes. [Reference: Journal of Medicinal Chemistry, 54(8), 2529–91]
  3. Walline CC, Nichols DE, Carroll FI, Barker EL (June 2008). “Uncovering the Molecular Insights into Serotonin Transporter Recognition.” Comparative molecular field analysis using selectivity fields revealed crucial residues in the serotonin transporter’s third transmembrane helix associated with substrate and antagonist recognition. [Reference: The Journal of Pharmacology and Experimental Therapeutics, 325(3), 791–800]
  4. Capela JP, Carmo H, Remião F, Bastos ML, Meisel A, Carvalho F (June 2009). “Understanding the Molecular Mechanisms of Ecstasy-Induced Neurotoxicity.” This comprehensive overview explores the molecular and cellular mechanisms behind the neurotoxic effects of ecstasy (MDMA). [Reference: Molecular Neurobiology, 39(3), 210–71]
  5. Sarkar S, Schmued L (August 2010). “A Comprehensive Look at Ecstasy (MDMA) Neurotoxicity.” This article provides a detailed overview of the neurotoxic effects of MDMA (Ecstasy). It delves into the complex mechanisms involved in MDMA-induced neurotoxicity. [Reference: Current Pharmaceutical Biotechnology, 11(5), 460–9]
  6. Escubedo E, Abad S, Torres I, Camarasa J, Pubill D (January 2011). “Comparative Neurochemical Profile of MDMA and Its Metabolite alpha-Methyldopamine.” This study offers a comparative analysis of the neurochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite alpha-methyldopamine on key targets related to MDMA neurotoxicity. [Reference: Neurochemistry International, 58(1), 92–101]

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