D2-MDMA

d2-MDMA, also known as d2-3,4-methylenedioxymethamphetamine or as deuterated-MDMA (D-MDMA), is an entactogen and stimulant of the phenethylamine, amphetamine, and MDxx families related to MDMA ("ecstasy").^{[1][2][3][4][5][6]} It is the deuterated isotopologue of MDMA in which the hydrogen atoms on the carbon atom of the 3,4-methylenedioxy ring have been replaced with the deuterium isotopes.^[1][2][6]

Other namesDeuterated-MDMA; D-MDMA; d2-3,4-Methylenedioxymethamphetamine; Deumidomafetamine; d2-Midomafetamine

Drug classEntactogen; Stimulant

ATC code

• None

PubChem CID

• 13909086

Quick facts Clinical data, Other names ...

d2-MDMA

Clinical data
Other names	Deuterated-MDMA; D-MDMA; d2-3,4-Methylenedioxymethamphetamine; Deumidomafetamine; d2-Midomafetamine
Drug class	Entactogen; Stimulant
ATC code	None
Identifiers
IUPAC name 1-(2,2-dideuterio-1,3-benzodioxol-5-yl)-N-methylpropan-2-amine
PubChem CID	13909086
Chemical and physical data
Formula	C11H15NO2
Molar mass	193.246 g·mol−1
3D model (JSmol)	Interactive image
SMILES [2H]C1(OC2=C(O1)C=C(C=C2)CC(C)NC)[2H]
InChI InChI=1S/C11H15NO2/c1-8(12-2)5-9-3-4-10-11(6-9)14-7-13-10/h3-4,6,8,12H,5,7H2,1-2H3/i7D2 Key:SHXWCVYOXRDMCX-RJSZUWSASA-N

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MDMA is known to produce serotonergic neurotoxicity and associated cognitive deficits and emotional and behavioral changes.^[1][2] The neurotoxicity of MDMA may be due in part to metabolism of MDMA via opening of the 3,4-methylenedioxy ring or O-demethylation to form catechol metabolites like 3,4-dihydroxyamphetamine (HHA; α-methyldopamine) and 3,4-dihydroxymethamphetamine (HHMA; α,N-dimethyldopamine).^[1][2] These metabolites may subsequently undergo further metabolism into reactive oxygen species (ROS) that damage serotonergic neurons.^[1][2] In relation to this, d2-MDMA is thought to be resistant to metabolism in this location due to the greater amount of energy required to break deuterium–carbon bonds compared to hydrogen–carbon bonds.^[1][2] As a result, d2-MDMA may have less neurotoxic potential than MDMA.^[1][2] On the other hand, whereas the pharmacokinetics and neurotoxicity of d2-MDMA may be altered compared to MDMA, it is thought that the drug will have similar or near-identical pharmacodynamics as MDMA, for instance interactions with monoamine transporters and serotonin receptors, aside from differing metabolites.^[1][2] Due to the reduced O-demethylation with d2-MDMA, N-demethylation into d2-MDA may instead predominate with this compound in contrast to MDMA.^[1]

d2-MDMA produces hyperlocomotion, stereotypy, and sensitization in rodents similarly to MDMA and with comparable potency.^[1] However, there were some slight differences between d2-MDMA and MDMA in terms of these effects at certain doses.^[1] In addition, d2-MDMA at high doses might be less lethal via serotonin syndrome in rodents than MDMA based on preliminary findings.^[1] d2-MDMA fully substitutes for MDMA in rodent drug discrimination tests and with equal potency and efficacy.^[2] The drug produced hyperthermia in rodents similarly to d2-MDMA, but this effect was shorter-lasting and of lower magnitude in comparison.^[2] However, this might have simply been related to potency differences in terms of this effect.^[2] The in-vitro pharmacodynamics and other effects of d2-MDMA have not yet been studied or reported.^[2]

d2-MDMA was studied by William E. Fantegrossi and colleagues and described by these researchers in 2017,^[3] 2018,^[4] and 2020.^[1][2] It is of potential interest for use in medicine as a better-tolerated and safer alternative to MDMA in the treatment of conditions like post-traumatic stress disorder (PTSD) and social anxiety disorder.^[1][2] On the other hand, d2-MDMA also has potential to emerge as a novel designer recreational drug.^[6] Deuterated analogues of MDMA have been patented by Nick Cozzi and Paul Daley of the Alexander Shulgin Research Institute (ASRI).^[7][8]