ArticleDrug metabolism and disposition: the biological fate of chemicals2014
Nonlinear pharmacokinetics of (+/-)3,4-methylenedioxymethamphetamine (MDMA) and its pharmacodynamic consequences in the rat.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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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.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Stereoselective, sex-dependent 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- A repeated low-dose regimen of MDMA has transient next-day effects on locomotor activity, anxiety-like behavior, and brain serotonin levels, with no effect on anhedonia-like behavior, in both female and male rats.Psychopharmacology · 2026Article
- Preclinical Systemic Pharmacokinetics, Dose Proportionality, and Central Nervous System Distribution of the ATM Inhibitor WSD0628, a Novel Radiosensitizer for the Treatment of Brain Tumors.The Journal of pharmacology and experimental therapeutics · 2024Article
- Brain Concentrations of MDPV and its Metabolites in Male Rats: Relationship to Pharmacodynamic Effects.Current pharmaceutical design · 2022Article
- Pharmacokinetics and pharmacodynamics of cyclopropylfentanyl in male rats.Psychopharmacology · 2021Article
- Evidence for nonlinear accumulation of the ultrapotent fentanyl analog, carfentanil, after systemic administration to male rats.Neuropharmacology · 2019Article
- Differential role of dose and environment in initiating and intensifying neurotoxicity caused by MDMA in rats.BMC pharmacology & toxicology · 2019Article
- Metabolites of the ring-substituted stimulants MDMA, methylone and MDPV differentially affect human monoaminergic systems.Journal of psychopharmacology (Oxford, England) · 2019Article
- A review of the influence of functional group modifications to the core scaffold of synthetic cathinones on drug pharmacokinetics.Psychopharmacology · 2019Review
- Pharmacodynamic Effects, Pharmacokinetics, and Metabolism of the Synthetic Cannabinoid AM-2201 in Male Rats.The Journal of pharmacology and experimental therapeutics · 2018Article
- Comparison of the effects of abstinence on MDMA and cocaine self-administration in rats.Psychopharmacology · 2018Article
- A Conserved Role for Serotonergic Neurotransmission in Mediating Social Behavior in Octopus.Current biology : CB · 2018Article
- Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs.Current topics in behavioral neurosciences · 2017Review
- Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-Frontiers in psychiatry · 2017Article
- Linear pharmacokinetics of 3,4-methylenedioxypyrovalerone (MDPV) and its metabolites in the rat: relationship to pharmacodynamic effects.Addiction biology · 2016Article
- New Insights on Different Response of MDMA-Elicited Serotonin Syndrome to Systemic and Intracranial Administrations in the Rat Brain.PloS one · 2016Article
- Mechanisms and environmental factors that underlying the intensification of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced serotonin syndrome in rats.Psychopharmacology · 2015Article
- Article
- Baths salts, spice, and related designer drugs: the science behind the headlines.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug that can cause severe and even fatal adverse effects. However, interest remains for its possible clinical applications in posttraumatic stress disorder and anxiety treatment. Preclinical studies to determine MDMA's safety are needed. We evaluated MDMA's pharmacokinetics and metabolism in male rats receiving 2.5, 5, and 10 mg/kg s.c. MDMA, and the associated pharmacodynamic consequences. Blood was collected via jugular catheter at 0, 0.5, 1, 2, 4, 6, 8, 16, and 24 hours, with simultaneous serotonin (5-HT) behavioral syndrome and core temperature monitoring. Plasma specimens were analyzed for MDMA and the metabolites (±)-3,4-dihydroxymethamphetamine (HHMA), (±)-4-hydroxy-3-methoxymethamphetamine (HMMA), and (±)-3,4-methylenedioxyamphetamine (MDA) by liquid chromatography-tandem mass spectrometry. After 2.5 mg/kg MDMA, mean MDMA Cmax was 164 ± 47.1 ng/ml, HHMA and HMMA were major metabolites, and <20% of MDMA was metabolized to MDA. After 5- and 10-mg/kg doses, MDMA areas under the curve (AUCs) were 3- and 10-fold greater than those after 2.5 mg/kg; HHMA and HMMA AUC values were relatively constant across doses; and MDA AUC values were greater than dose-proportional. Our data provide decisive in vivo evidence that MDMA and MDA display nonlinear accumulation via metabolic autoinhibition in the rat. Importantly, 5-HT syndrome severity correlated with MDMA concentrations (r = 0.8083; P < 0.0001) and core temperature correlated with MDA concentrations (r = 0.7595; P < 0.0001), suggesting that MDMA's behavioral and hyperthermic effects may involve distinct mechanisms. Given key similarities between MDMA pharmacokinetics in rats and humans, data from rats can be useful when provided at clinically relevant doses.
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Registered trials
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