Direct comparison of (±) 3,4-methylenedioxymethamphetamine ("ecstasy") disposition and metabolism in squirrel monkeys and humans

Melanie Mueller, Erin A. Kolbrich, Frank T. Peters, Hans H. Maurer, Una D McCann, Marilyn A. Huestis, George Ricaurte

Research output: Contribution to journalArticle

Abstract

The present study compared the disposition and metabolism of the recreational drug (±) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4- methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.

Original languageEnglish (US)
Pages (from-to)367-373
Number of pages7
JournalTherapeutic Drug Monitoring
Volume31
Issue number3
DOIs
StatePublished - Jun 2009

Fingerprint

N-Methyl-3,4-methylenedioxyamphetamine
Saimiri
3,4-Methylenedioxyamphetamine
Street Drugs
Liquid Chromatography
Half-Life
Pharmacokinetics

Keywords

  • MDMA
  • MDMA metabolites
  • Neurotoxicity
  • Nonlinear pharmacokinetics
  • Serotonin
  • Squirrel monkey

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Direct comparison of (±) 3,4-methylenedioxymethamphetamine ("ecstasy") disposition and metabolism in squirrel monkeys and humans. / Mueller, Melanie; Kolbrich, Erin A.; Peters, Frank T.; Maurer, Hans H.; McCann, Una D; Huestis, Marilyn A.; Ricaurte, George.

In: Therapeutic Drug Monitoring, Vol. 31, No. 3, 06.2009, p. 367-373.

Research output: Contribution to journalArticle

Mueller, Melanie ; Kolbrich, Erin A. ; Peters, Frank T. ; Maurer, Hans H. ; McCann, Una D ; Huestis, Marilyn A. ; Ricaurte, George. / Direct comparison of (±) 3,4-methylenedioxymethamphetamine ("ecstasy") disposition and metabolism in squirrel monkeys and humans. In: Therapeutic Drug Monitoring. 2009 ; Vol. 31, No. 3. pp. 367-373.
@article{4d03710f2a86468bac6b5d9be6daf781,
title = "Direct comparison of (±) 3,4-methylenedioxymethamphetamine ({"}ecstasy{"}) disposition and metabolism in squirrel monkeys and humans",
abstract = "The present study compared the disposition and metabolism of the recreational drug (±) 3,4-methylenedioxymethamphetamine (MDMA, {"}ecstasy{"}) in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4- methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.",
keywords = "MDMA, MDMA metabolites, Neurotoxicity, Nonlinear pharmacokinetics, Serotonin, Squirrel monkey",
author = "Melanie Mueller and Kolbrich, {Erin A.} and Peters, {Frank T.} and Maurer, {Hans H.} and McCann, {Una D} and Huestis, {Marilyn A.} and George Ricaurte",
year = "2009",
month = "6",
doi = "10.1097/FTD.0b013e3181a4f6c2",
language = "English (US)",
volume = "31",
pages = "367--373",
journal = "Therapeutic Drug Monitoring",
issn = "0163-4356",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Direct comparison of (±) 3,4-methylenedioxymethamphetamine ("ecstasy") disposition and metabolism in squirrel monkeys and humans

AU - Mueller, Melanie

AU - Kolbrich, Erin A.

AU - Peters, Frank T.

AU - Maurer, Hans H.

AU - McCann, Una D

AU - Huestis, Marilyn A.

AU - Ricaurte, George

PY - 2009/6

Y1 - 2009/6

N2 - The present study compared the disposition and metabolism of the recreational drug (±) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4- methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.

AB - The present study compared the disposition and metabolism of the recreational drug (±) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4- methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.

KW - MDMA

KW - MDMA metabolites

KW - Neurotoxicity

KW - Nonlinear pharmacokinetics

KW - Serotonin

KW - Squirrel monkey

UR - http://www.scopus.com/inward/record.url?scp=67651113953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67651113953&partnerID=8YFLogxK

U2 - 10.1097/FTD.0b013e3181a4f6c2

DO - 10.1097/FTD.0b013e3181a4f6c2

M3 - Article

C2 - 19417716

AN - SCOPUS:67651113953

VL - 31

SP - 367

EP - 373

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 3

ER -