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.[1][2][3]
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.[4] 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,[5][6][7] making it unclear how much less neurotoxic DFMDA and related drugs would be in practice.
^Meanwell NA (March 2011). "Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design". Journal of Medicinal Chemistry. 54 (8): 2529–91.
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^Sarkar S, Schmued L (August 2010). "Neurotoxicity of ecstasy (MDMA): an overview". Current Pharmaceutical Biotechnology. 11 (5): 460–9.
doi:
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PMID20420572.
^Escubedo E, Abad S, Torres I, Camarasa J, Pubill D (January 2011). "Comparative neurochemical profile of 3,4-methylenedioxymethamphetamine and its metabolite alpha-methyldopamine on key targets of MDMA neurotoxicity". Neurochemistry International. 58 (1): 92–101.
doi:
10.1016/j.neuint.2010.11.001.
PMID21074589.
S2CID2853533.