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Identification
Name3,4-Methylenedioxymethamphetamine
Accession NumberDB01454
Typesmall molecule
Groupsexperimental, illicit
Description

An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
EcstasyNot AvailableNot Available
MDMANot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number42542-10-9
WeightAverage: 193.2423
Monoisotopic: 193.110278729
Chemical FormulaC11H15NO2
InChI KeySHXWCVYOXRDMCX-UHFFFAOYSA-N
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
IUPAC Name
[1-(2H-1,3-benzodioxol-5-yl)propan-2-yl](methyl)amine
SMILES
CNC(C)CC1=CC2=C(OCO2)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenethylamines
Direct parentAmphetamines and Derivatives
Alternative parentsBenzodioxoles; Alkyl Aryl Ethers; Polyamines; Dialkylamines; Acetals
Substituentsalkyl aryl ether; secondary amine; secondary aliphatic amine; acetal; polyamine; ether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Pharmacology
IndicationClinical trials are now testing the therapeutic potential of MDMA for post-traumatic stress disorder (PTSD) and anxiety associated with terminal cancer. MDMA is one of the four most widely used illicit drugs in the U.S.
PharmacodynamicsMDMA acts as a releasing agent of serotonin, norepinephrine, and dopamine.
Mechanism of actionIt enters neurons via carriage by the monoamine transporters. Once inside, MDMA inhibits the vesicular monoamine transporter, which results in increased concentrations of serotonin, norepinephrine, and dopamine into the cytoplasm, and induces their release by reversing their respective transporters through a process known as phosphorylation. It also acts as a weak 5-HT1 and 5-HT2 receptor agonist. MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin secretion via activation of the serotonin system. Oxytocin is a hormone released following events like hugging, orgasm, and childbirth, and is thought to facilitate bonding and the establishment of trust. Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin 5-HT1A receptor.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic: CYP450 extensively involved, especially CYP2D6 MDMA is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine. The metabolism may be primarily by cytochrome P450 (CYP450) enzymes (CYP2D6 (in humans, but CYP2D1 in mice), and CYP3A4) and COMT. Complex, nonlinear pharmacokinetics arise via autoinhibition of CYP2D6 and CYP2D8, resulting in zeroth order kinetics at higher doses. It is thought that this can result in sustained and higher concentrations of MDMA if the user takes consecutive doses of the drug.

Route of eliminationrenal
Half life6–10 (though duration of effects is typically actually 3–5 hours)
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9639
Caco-2 permeable + 0.6781
P-glycoprotein substrate Non-substrate 0.6447
P-glycoprotein inhibitor I Non-inhibitor 0.8631
P-glycoprotein inhibitor II Non-inhibitor 0.8926
Renal organic cation transporter Non-inhibitor 0.7568
CYP450 2C9 substrate Non-substrate 0.8507
CYP450 2D6 substrate Non-substrate 0.5776
CYP450 3A4 substrate Non-substrate 0.5325
CYP450 1A2 substrate Inhibitor 0.7626
CYP450 2C9 substrate Non-inhibitor 0.8324
CYP450 2D6 substrate Inhibitor 0.7708
CYP450 2C19 substrate Non-inhibitor 0.6331
CYP450 3A4 substrate Non-inhibitor 0.6106
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5857
Ames test Non AMES toxic 0.6597
Carcinogenicity Non-carcinogens 0.9001
Biodegradation Ready biodegradable 0.5643
Rat acute toxicity 2.7501 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9585
hERG inhibition (predictor II) Non-inhibitor 0.9417
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility3.22e+00 g/lALOGPS
logP1.65ALOGPS
logP1.86ChemAxon
logS-1.8ALOGPS
pKa (strongest basic)10.14ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area30.49ChemAxon
rotatable bond count3ChemAxon
refractivity54.25ChemAxon
polarizability21.49ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Freudenmann RW, Oxler F, Bernschneider-Reif S: The origin of MDMA (ecstasy) revisited: the true story reconstructed from the original documents. Addiction. 2006 Sep;101(9):1241-5. Pubmed
  2. Jayanthi LD, Ramamoorthy S: Regulation of monoamine transporters: influence of psychostimulants and therapeutic antidepressants. AAPS J. 2005 Oct 27;7(3):E728-38. Pubmed
  3. Verrico CD, Miller GM, Madras BK: MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology (Berl). 2007 Jan;189(4):489-503. Epub 2005 Oct 12. Pubmed
External Links
ResourceLink
KEGG CompoundC07577
PubChem Compound1615
PubChem Substance46506404
ChemSpider1556
ChEBI1391
ChEMBL
PharmGKBPA131887008
Wikipedia3,4-Methylenedioxymethamphetamine
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Sodium-dependent serotonin transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: negative modulator

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

References:

  1. Shankaran M, Yamamoto BK, Gudelsky GA: Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine. Eur J Pharmacol. 1999 Dec 3;385(2-3):103-10. Pubmed
  2. Whitworth TL, Herndon LC, Quick MW: Psychostimulants differentially regulate serotonin transporter expression in thalamocortical neurons. J Neurosci. 2002 Jan 1;22(1):RC192. Pubmed
  3. Szabo Z, McCann UD, Wilson AA, Scheffel U, Owonikoko T, Mathews WB, Ravert HT, Hilton J, Dannals RF, Ricaurte GA: Comparison of (+)-(11)C-McN5652 and (11)C-DASB as serotonin transporter radioligands under various experimental conditions. J Nucl Med. 2002 May;43(5):678-92. Pubmed
  4. Boot BP, Mechan AO, McCann UD, Ricaurte GA: MDMA- and p-chlorophenylalanine-induced reduction in 5-HT concentrations: effects on serotonin transporter densities. Eur J Pharmacol. 2002 Oct 25;453(2-3):239-44. Pubmed
  5. Saldana SN, Barker EL: Temperature and 3,4-methylenedioxymethamphetamine alter human serotonin transporter-mediated dopamine uptake. Neurosci Lett. 2004 Jan 16;354(3):209-12. Pubmed
  6. Bogen IL, Haug KH, Myhre O, Fonnum F: Short- and long-term effects of MDMA (“ecstasy”) on synaptosomal and vesicular uptake of neurotransmitters in vitro and ex vivo. Neurochem Int. 2003 Sep-Oct;43(4-5):393-400. Pubmed

2. Synaptic vesicular amine transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Synaptic vesicular amine transporter Q05940 Details

References:

  1. Biezonski DK, Meyer JS: Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity. J Neurochem. 2010 Feb;112(4):951-62. Epub 2009 Nov 30. Pubmed
  2. Hansen JP, Riddle EL, Sandoval V, Brown JM, Gibb JW, Hanson GR, Fleckenstein AE: Methylenedioxymethamphetamine decreases plasmalemmal and vesicular dopamine transport: mechanisms and implications for neurotoxicity. J Pharmacol Exp Ther. 2002 Mar;300(3):1093-100. Pubmed

3. Sodium-dependent dopamine transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: negative modulator

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

References:

  1. Hansen JP, Riddle EL, Sandoval V, Brown JM, Gibb JW, Hanson GR, Fleckenstein AE: Methylenedioxymethamphetamine decreases plasmalemmal and vesicular dopamine transport: mechanisms and implications for neurotoxicity. J Pharmacol Exp Ther. 2002 Mar;300(3):1093-100. Pubmed
  2. Fitzgerald JL, Reid JJ: Effects of methylenedioxymethamphetamine on the release of monoamines from rat brain slices. Eur J Pharmacol. 1990 Nov 27;191(2):217-20. Pubmed
  3. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR: New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-98. Pubmed

4. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

References:

  1. Lyon RA, Glennon RA, Titeler M: 3,4-Methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT1 and 5-HT2 receptors. Psychopharmacology (Berl). 1986;88(4):525-6. Pubmed
  2. Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA: Effect of the R(-) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors. Neurosci Lett. 1994 Aug 15;177(1-2):111-5. Pubmed

5. 5-hydroxytryptamine receptor 2B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2B P41595 Details

References:

  1. Lyon RA, Glennon RA, Titeler M: 3,4-Methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT1 and 5-HT2 receptors. Psychopharmacology (Berl). 1986;88(4):525-6. Pubmed

6. 5-hydroxytryptamine receptor 2C

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

References:

  1. Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA: Effect of the R(-) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors. Neurosci Lett. 1994 Aug 15;177(1-2):111-5. Pubmed
  2. Lyon RA, Glennon RA, Titeler M: 3,4-Methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT1 and 5-HT2 receptors. Psychopharmacology (Berl). 1986;88(4):525-6. Pubmed

7. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: negative modulator

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

References:

  1. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. Pubmed
  2. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR: New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-98. Pubmed
  3. Haughey HM, Brown JM, Wilkins DG, Hanson GR, Fleckenstein AE: Differential effects of methamphetamine on Na(+)/Cl(-)-dependent transporters. Brain Res. 2000 Apr 28;863(1-2):59-65. Pubmed

Transporters

1. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

References:

  1. Verrico CD, Miller GM, Madras BK: MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology (Berl). 2007 Jan;189(4):489-503. Epub 2005 Oct 12. Pubmed

2. Sodium-dependent dopamine transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

References:

  1. Verrico CD, Miller GM, Madras BK: MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology (Berl). 2007 Jan;189(4):489-503. Epub 2005 Oct 12. Pubmed

3. Sodium-dependent serotonin transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

References:

  1. Verrico CD, Miller GM, Madras BK: MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology (Berl). 2007 Jan;189(4):489-503. Epub 2005 Oct 12. Pubmed

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Drug created on July 31, 2007 07:09 / Updated on September 16, 2013 17:14