Evidence map›Paper›PMID 36700960›Full record

ArticlePsychopharmacology2023

Dantrolene sodium fails to reverse robust brain hyperthermia induced by MDMA and methamphetamine in rats.

Keaton T Cameron-Burr, R Aaron Bola, Eugene A Kiyatkin

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

Article in Psychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 28% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

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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

3 authors at 1 institution in 1 country.

Keaton T Cameron-BurrBehavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS, 251 Bayview Blvd, Baltimore, MD, 21224, USA.
R Aaron BolaBehavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS, 251 Bayview Blvd, Baltimore, MD, 21224, USA.
Eugene A KiyatkinBehavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS, 251 Bayview Blvd, Baltimore, MD, 21224, USA. ekiyatki@intra.nida.nih.gov.ORCID http://orcid.org/0000-0002-3744-0873
National Institutes of Health · US

Funding

Electrophysiological and electrochemical studues of addictive drugsZIADA000566 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI KIYATKIN, EUGENE A · 2010 to 2025
$10.1M
Brain Temperature, Reward, And Drugs Of AbuseZIADA000445 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI KIYATKIN, EUGENE A · 2009 to 2020
$4.1M
Intramural NIH HHS ZIA DA000445Intramural NIH HHS ZIA DA000566NIDA NIH HHS 1ZIADA000566-03
6 · The paper itself

Abstract

rationaleHyperthermia induced by psychomotor stimulants may cause leakage of the blood-brain barrier, vasogenic edema, and lethality in extreme cases. Current treatments such as whole-body cooling are only symptomatic and a clear need to develop pharmacological interventions exists. Dantrolene sodium, a peripheral muscle relaxant used in the treatment of malignant hyperthermia, has been proposed as potentially effective to treat MDMA-hyperthermia in emergency rooms. However, debate around its efficacy for this indication persists.

objectivesTo investigate dantrolene as a treatment for illicit hyperthermia induced by psychomotor stimulant drugs, we examined how Ryanodex®, a concentrated formulation of dantrolene sodium produced by Eagle Pharmaceuticals, influences 3,4-methylenedioxymethamphetamine (MDMA)- and methamphetamine (METH)-induced hyperthermia in awake freely moving rats. We injected rats with moderate doses of MDMA (9 mg/kg) and METH (9 mg/kg) and administered Ryanodex® intravenously (6 mg/kg) after the development of robust hyperthermia (>2.5 °C) mimicking clinical acute intoxication. We conducted simultaneous temperature recordings in the brain, temporal muscle, and skin to determine the basic mechanisms underlying temperature responses. To assess the efficacy of dantrolene in attenuating severe hyperthermia, we administered MDMA to rats maintained in a warm ambient environment (29 °C), conditions which produce robust brain and body hyperthermia (>40 °C) and lethality.

resultsDantrolene failed to attenuate MDMA- and METH-induced hyperthermia, though locomotor activity was significantly reduced. All animals maintained at warm ambient temperatures that received dantrolene during severe drug-induced hyperthermia died within or soon after the recording session.

conclusionsOur results suggest that dantrolene sodium formulations are not mechanistically suited to treat MDMA- and METH-induced hyperthermia.

Indexed as

HyperthermiaMethamphetamineN-Methyl-3,4-methylenedioxyamphetamineAnimalsBody TemperatureBrainDantroleneRatsDantroleneMethamphetamineN-Methyl-3,4-methylenedioxyamphetamineDrug abuseEcstasyOverdosePsychomotor stimulantTranslational

Identifiers

PMID36700960
PMCPMC12288437
OpenAlexW4318054810

What OpenQuestion holds

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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.