Ambient temperature effects on 3,4-methylenedioxymethamphetamine-induced thermodysregulation and pharmacokinetics in male monkeys.
Matthew L Banks, Jon E. Sprague, David F Kisor, Paul W Czoty, David E Nichols, Michael A Nader
Drug Metabolism and Disposition October 2007 DOI: 10.1124/dmd.107.016261 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Sample size | 19 |
| Population | Monkeys |
| Intervention | MDMA |
| Dose | 1.5 mg/kg i.v. |
| Duration | 240 minutes |
| Topics | MDMA |
| Key findings | MDMA induced hypothermia at 18°C, hyperthermia at 31°C, and no change at 24°C. MDMA half-life was longer at 18°C and 31°C than at 24°C, and cool temperature increased MDA exposure, suggesting altered disposition. |
Abstract
Changes in ambient temperature are known to alter both the hyperthermic and the serotonergic consequences of 3,4-methylenedioxymethamphetamine (MDMA). Metabolism of MDMA has been suggested to be a requisite for these neurotoxic effects, whereas the hyperthermic response is an important contributing variable. The aim of the present study was to investigate the interaction between ambient temperature, MDMA-induced thermodysregulation, and its metabolic disposition in monkeys. MDMA (1.5 mg/kg i.v.) was administered noncontingently at cool (18 degrees C; n = 5), room (24 degrees C; n = 7), and warm (31 degrees C; n = 7) ambient temperatures. For 240 min following MDMA administration, core temperature was recorded and blood samples were collected for analysis of MDMA and its metabolites 3,4-dihydroxymethamphetamine (HHMA), 3,4-dihydroxyamphetamine, and 3,4-methylenedioxyamphetamine (MDA). A dose of 1.5 mg/kg MDMA induced a hypothermic response at 18 degrees C, a hyperthermic response at 31 degrees C, and did not significantly change core temperature at 24 degrees C. Regardless of ambient temperature, plasma MDMA concentrations reached maximum within 5 min, and HHMA was a major metabolite. Curiously, the approximate elimination half-life (t(1/2)) of MDMA at 18 degrees C (136 min) and 31 degrees C (144 min) was increased compared with 24 degrees C (90 min) and is most likely because of volume of distribution changes induced by core temperature alterations. At 18 degrees C, there was a significantly higher MDA area under the concentration-time curve (AUC) and a trend for a lower HHMA AUC compared with 24 degrees C and 31 degrees C, suggesting that MDMA disposition was altered. Overall, induction of hypothermia in a cool environment by MDMA may alter its disposition. These results could have implications for MDMA-induced serotonergic consequences.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 19
- The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives British Journal of Pharmacology March 3, 2010
- In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys. Experimental and Clinical Psychopharmacology February 1, 2008
- 3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner Neuropsychopharmacology September 1, 2017
- Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) and R(-) MDMA on actigraphy-based daytime activity and sleep parameters in rhesus monkeys. Experimental and Clinical Psychopharmacology June 25, 2018
- From Bench to Bedside: Understanding the Science behind the Pharmacologic Management of MDMA- and other Sympathomimetic-Mediated Hyperthermia Journal of Pharmacy Technology May 1, 2011
and 14 more in the library
Cites 14
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- MDMA (Ecstasy) and the Rave: A Review Pediatrics October 1, 1997
- The Role of Metabolism in 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylenedioxymethamphetamine (Ecstasy) toxicity Therapeutic Drug Monitoring March 19, 2004
- Cutaneous Vasoconstriction Contributes to Hyperthermia Induced by 3,4-Methylenedioxymethamphetamine (Ecstasy) in Conscious Rabbits Journal of Neuroscience November 1, 2001
and 9 more in the library