Effects of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) and para-methoxyamphetamine on striatal 5-HT when co-administered with moclobemide
Alexander Freezer, Abdallah Salem, Rodney J. Irvine
Brain Research March 8, 2005 DOI: 10.1016/j.brainres.2005.01.093 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Moclobemide MDMA PMA |
| Dose | 20 mg/kg moclobemide, 10 mg/kg MDMA or PMA |
| Duration | 5 hours |
| Topics | MDMA Serotonin |
| Keywords | Moclobemide Pharmacology Microdialysis Monoamine neurotransmitter 5-HT Receptor Monoamine oxidase inhibitor Extracellular |
| Citations | 34 |
| Key findings | Co-administration of MDMA with moclobemide increased extracellular serotonin to 980% of baseline, exceeding the increase from MDMA alone (590%) and suggesting enhanced serotonin-related toxicity. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") and para-methoxyamphetamine (PMA) are commonly used recreational drugs. PMA, often mistaken for MDMA, is reported to be more toxic in human use than MDMA. Both of these drugs have been shown to facilitate the release and prevent the reuptake of 5-hydroxytryptamine (5-HT, serotonin). PMA is also a potent inhibitor of monoamine oxidase type A (MAO-A), an enzyme responsible for the catabolism of 5-HT, and this characteristic may contribute to its increased toxicity. In humans, co-administration of MDMA with the reversible MAO-A inhibitor moclobemide has led to increased apparent toxicity with ensuing fatalities. In the present study, using microdialysis, we examined the effects of co-administration of MDMA and PMA with moclobemide on extracellular concentrations of 5-HT and 5-hydroxy indol acetic acid (5-HIAA) in the striatum of the rat. 5-HT-mediated effects on body temperature and behavior were also recorded. Rats were pretreated with saline or 20 mg/kg (i.p.) moclobemide and 60 min later injected with 10 mg/kg MDMA, PMA, or saline. Dialysate samples were collected every 30 min for 5 h and analyzed by HPLC-ED. Both MDMA and PMA produced significant increases in extracellular 5-HT concentrations (590% and 360%, respectively, P < 0.05). Rats treated with PMA and MDMA displayed significantly increased 5-HT-related behaviors (P < 0.05). Furthermore, only MDMA was capable of producing additional significant increases in 5-HT concentrations (980%, P < 0.05) when co-administered with moclobemide. These data suggest that co-administration of MDMA with moclobemide increases extracellular 5-HT and 5-HT-mediated behaviors and may cause increased 5-HT related toxicity similar to that reported with PMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 8
- Qualitative Review of Serotonin Syndrome, Ecstasy (MDMA) and the use of Other Serotonergic Substances: Hierarchy of Risk Australian & New Zealand Journal of Psychiatry July 25, 2007
- Serotonin toxicity involving MDMA (ecstasy) and moclobemide Forensic Science International May 20, 2011
- Deaths Involving MDMA and the Concomitant Use of Pharmaceutical Drugs Journal of Analytical Toxicology May 1, 2011
- Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish Brain Sciences August 25, 2020
- Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data. CNS Drugs January 17, 2026
and 3 more in the library
Cites 10
- Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions Journal of Neurochemistry 1996
- 5‐HT loss in rat brain following 3, 4‐methylenedioxymethamphetamine (MDMA), p‐chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine British Journal of Pharmacology March 1, 1993
- Death following ingestion of MDMA (ecstasy) and moclobemide Addiction February 20, 2003
- Comparative Effects of Substituted Amphetamines (PMA, MDMA, and METH) on Monoamines in Rat Caudate Annals of the New York Academy of Sciences June 1, 2002
- The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacological Reviews September 2003
and 5 more in the library