Difluoromethylenedioxyamphetamine (DFMDA) is a substituted derivative of 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

Methylenedioxy

Methylenedioxy in the field of chemistry, particularly in organic chemistry, is the name for a functional group with the structural formula R-O-CH2-O-R' which is connected to the rest of a molecule by two chemical bonds. The methylenedioxy group consists of two oxygen atoms connected to a methylene...

 ring, producing neurotoxic metabolites such as alpha-Methyldopamine

Alpha-Methyldopamine

α-Methyldopamine , also known as 3,4-dihydroxyamphetamine , is a neurotoxin and research chemical of the phenethylamine and amphetamine chemical classes...

, it was hoped that the difluoromethylenedioxy bioisostere

Bioisostere

In medicinal chemistry, bioisosteres are substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to a chemical compound. In drug design, the purpose of exchanging one bioisostere for another is to enhance the desired biological or...

 would show increased metabolic stability and less toxicity.

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

Serotonin transporter

The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 affinity in between that of MDA and MDMA. However there is known to be a lack of bulk tolerance at this position of the molecule, shown by the generally reduced activity of the ethylidenedioxy

Ethylidenedioxyamphetamine

Ethylidenedioxyamphetamine is a substituted derivative of methylenedioxyamphetamine , which was developed by David Nichols and coworkers, in the course of research to determine the bulk tolerance around the benzodioxole portion of the MDA molecule...

 and isopropylidenedioxy analogues. 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, making it unclear how much less neurotoxic DFMDA and related drugs would be in practice.

See also

• 6-APB
  6-APB
  6-benzofuran or 1-benzofuran-6-ylpropan-2-amine is thought to be a stimulant and entactogen drug although to date, no authoritative source can say even whether or not it is psychoactive. Chemically, it is of the phenethylamine and substituted amphetamine classes...
  
  
• EDA
  Ethylidenedioxyamphetamine
  Ethylidenedioxyamphetamine is a substituted derivative of methylenedioxyamphetamine , which was developed by David Nichols and coworkers, in the course of research to determine the bulk tolerance around the benzodioxole portion of the MDA molecule...
  
  
• IAP
• MDAI