Evidence map›Paper›PMID 19628751›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2009

Further studies on the role of metabolites in (+/-)-3,4-methylenedioxymethamphetamine-induced serotonergic neurotoxicity.

Melanie Mueller, Jie Yuan, Anne Felim, Anne Neudörffer, Frank T Peters, Hans H Maurer, Una D McCann, Martine Largeron, George A Ricaurte

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
5.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 53 citations in OpenAlex.

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  14. Determination of the role of calcium on instability of neurotoxic metabolite of ecstasy by HPTLC-mass.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2013
    Article
  15. 3,4-methylenedioxymethamphetamine (MDMA): current perspectives.Substance abuse and rehabilitation · 2013
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Melanie MuellerDepartment of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA. ricaurte@jhmi.edu
Jie Yuan
Anne Felim
Anne Neudörffer
Frank T Peters
Hans H Maurer
Una D McCann
Martine Largeron
George A Ricaurte
Johns Hopkins University · USCentre National de la Recherche Scientifique · FRSaarland University · DE

Funding

NDMA NEUROTOXICITY--PERMANENT OR TRANSIENTR01DA005707 · NIDA · JOHNS HOPKINS UNIVERSITY · PI RICAURTE, GEORGE A · 1995 to 2005
$1.6M
PET Studies of the SERT and DAT in METH UsersR01DA025686 · NIDA · JOHNS HOPKINS UNIVERSITY · PI MCCANN, UNA D · 2010 to 2013
$1.5M
MDMA NEUROTOXICITY IN PRIMATE: PERMANENT OR TRANSIENT?R29DA005707 · NIDA · JOHNS HOPKINS UNIVERSITY · PI RICAURTE, GEORGE A · 1989 to 1993
–
NIDA NIH HHS DA01796401NIDA NIH HHS DA05707NIDA NIH HHS R01 DA025686
6 · The paper itself

Abstract

The mechanism by which the recreational drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA) destroys brain serotonin (5-HT) axon terminals is not understood. Recent studies have implicated MDMA metabolites, but their precise role remains unclear. To further evaluate the relative importance of metabolites versus the parent compound in neurotoxicity, we explored the relationship between pharmacokinetic parameters of MDMA, 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymethamphetamine (HHMA), and 4-hydroxy-3-methoxymethamphetamine (HMMA) and indexes of serotonergic neurotoxicity in the same animals. We also further evaluated the neurotoxic potential of 5-(N-acetylcystein-S-yl)-HHMA (5-NAC-HHMA), an MDMA metabolite recently implicated in 5-HT neurotoxicity. Lasting serotonergic deficits correlated strongly with pharmacokinetic parameters of MDMA (C(max) and area under the concentration-time curve), more weakly with those of MDA, and not at all with those of HHMA or HMMA (total amounts of the free analytes obtained after conjugate cleavage). HHMA and HMMA could not be detected in the brains of animals with high brain MDMA concentrations and high plasma HHMA and HMMA concentrations, suggesting that HHMA and HMMA do not readily penetrate the blood-brain barrier (either in their free form or as sulfate or glucuronic conjugates) and that little or no MDMA is metabolized to HHMA or HMMA in the brain. Repeated intraparenchymal administration of 5-NAC-HHMA did not produce significant lasting serotonergic deficits in the rat brain. Taken together, these results indicate that MDMA and, possibly, MDA are more important determinants of brain 5-HT neurotoxicity in the rat than HHMA and HMMA and bring into question the role of metabolites (including 5-NAC-HHMA) in MDMA neurotoxicity.

Indexed as

3,4-MethylenedioxyamphetamineAnimalsDeoxyepinephrineDisease Models, AnimalMaleNeurotoxicity SyndromesN-Methyl-3,4-methylenedioxyamphetamineRatsRats, Sprague-DawleySerotonin3,4-Methylenedioxyamphetaminealpha-methylepinineDeoxyepinephrineN-Methyl-3,4-methylenedioxyamphetamineSerotonin

Identifiers

PMID19628751
PMCPMC2769035
OpenAlexW1968135120

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.