PMID- 36700960
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230315
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 240
IP  - 4
DP  - 2023 Apr
TI  - Dantrolene sodium fails to reverse robust brain hyperthermia induced by MDMA and 
      methamphetamine in rats.
PG  - 785-795
LID - 10.1007/s00213-023-06321-x [doi]
AB  - RATIONALE: Hyperthermia 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. OBJECTIVES: To 
      investigate dantrolene as a treatment for illicit hyperthermia induced by 
      psychomotor stimulant drugs, we examined how Ryanodex(R), 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(R) intravenously (6 
      mg/kg) after the development of robust hyperthermia (>2.5  degrees 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  degrees C), conditions which produce robust brain and body hyperthermia 
      (>40  degrees C) and lethality. RESULTS: Dantrolene 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. CONCLUSIONS: Our results suggest that dantrolene sodium formulations are 
      not mechanistically suited to treat MDMA- and METH-induced hyperthermia.
CI  - (c) 2023. This is a U.S. Government work and not under copyright protection in the 
      US; foreign copyright protection may apply.
FAU - Cameron-Burr, Keaton T
AU  - Cameron-Burr KT
AD  - Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural 
      Research Program, National Institutes of Health, DHHS, 251 Bayview Blvd, 
      Baltimore, MD, 21224, USA.
FAU - Bola, R Aaron
AU  - Bola RA
AD  - Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural 
      Research Program, National Institutes of Health, DHHS, 251 Bayview Blvd, 
      Baltimore, MD, 21224, USA.
FAU - Kiyatkin, Eugene A
AU  - Kiyatkin EA
AUID- ORCID: 0000-0002-3744-0873
AD  - Behavioral 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.
LA  - eng
GR  - 1ZIADA000566-03/DA/NIDA NIH HHS/United States
GR  - 1ZIADA000566-03/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20230126
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - 44RAL3456C (Methamphetamine)
RN  - F64QU97QCR (Dantrolene)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *N-Methyl-3,4-methylenedioxyamphetamine
MH  - *Methamphetamine
MH  - Dantrolene/pharmacology
MH  - Body Temperature
MH  - Brain
MH  - *Hyperthermia, Induced
OTO - NOTNLM
OT  - Drug abuse
OT  - Ecstasy
OT  - Overdose
OT  - Psychomotor stimulant
OT  - Translational
EDAT- 2023/01/27 06:00
MHDA- 2023/03/15 06:00
CRDT- 2023/01/26 11:13
PHST- 2022/10/26 00:00 [received]
PHST- 2023/01/19 00:00 [accepted]
PHST- 2023/01/27 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/01/26 11:13 [entrez]
AID - 10.1007/s00213-023-06321-x [pii]
AID - 10.1007/s00213-023-06321-x [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2023 Apr;240(4):785-795. doi: 
      10.1007/s00213-023-06321-x. Epub 2023 Jan 26.