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targets (7) transporters (3)
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Identification
Name 3,4-Methylenedioxymethamphetamine
Accession Number DB01454
Type small molecule
Groups illicit, experimental
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Ecstasy
MDMA
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Adrenergic Uptake Inhibitors
  • Hallucinogens
  • Serotonin Agents
CAS number 42542-10-9
Weight Average: 193.2423
Monoisotopic: 193.110278729
Chemical Formula C11H15NO2
InChI Key InChIKey=SHXWCVYOXRDMCX-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
Plain Text
IUPAC Name
[1-(2H-1,3-benzodioxol-5-yl)propan-2-yl](methyl)amine
SMILES
CNC(C)CC1=CC2=C(OCO2)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amphetamines
  • Catecholamines and Derivatives
Substructures
  • Acetals and Derivatives
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Dioxoles
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzodioxoles
  • Anisoles
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
Pharmacology
Indication Clinical 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.
Pharmacodynamics MDMA acts as a releasing agent of serotonin, norepinephrine, and dopamine.
Mechanism of action It 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not 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 elimination renal
Half life 6–10 (though duration of effects is typically actually 3–5 hours)
Clearance Not Available
Toxicity Not Available
Affected organisms Not Available
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 3.22e+00 g/l ALOGPS
logP 1.65 ALOGPS
logP 1.86 ChemAxon
logS -1.8 ALOGPS
pKa (strongest basic) 10.14 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 30.49 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 54.25 ChemAxon
polarizability 21.49 ChemAxon
References
Synthesis Reference Not 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
Resource Link
KEGG Compound C07577 Link_out
PubChem Compound 1615 Link_out
PubChem Substance 46506404 Link_out
ChemSpider 1556 Link_out
ChEBI 1391 Link_out
ChEMBL 1391 Link_out
PharmGKB PA131887008 Link_out
Wikipedia http://en.wikipedia.org/wiki/3,4-Methylenedioxymethamphetamine Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Sodium-dependent serotonin transporter

Pharmacological action: yes
Actions: negative modulator

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis

Organism class: human
UniProt ID: Q05940 Link_out
Gene: SLC18A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: negative modulator

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: Q01959 Link_out
Gene: SLC6A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 2A receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 2B receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P41595 Link_out
Gene: HTR2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 2C receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: negative modulator

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

UniProt ID: Q01959 Link_out
Gene: SLC6A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on July 31, 2007 07:09 / Updated on February 17, 2013 16:27