PMID- 31954950
OWN - NLM
STAT- MEDLINE
DCOM- 20210118
LR  - 20210118
IS  - 1879-0046 (Electronic)
IS  - 0376-8716 (Linking)
VI  - 208
DP  - 2020 Mar 1
TI  - In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated 
      form in rodents: Drug discrimination and thermoregulation.
PG  - 107850
LID - S0376-8716(20)30015-6 [pii]
LID - 10.1016/j.drugalcdep.2020.107850 [doi]
AB  - BACKGROUND: Recent clinical studies support the use of 
      3,4-methylenedioxymethamphetamine (MDMA) as an adjunct treatment for 
      posttraumatic stress disorder (PTSD). Despite these promising findings, MDMA 
      administration in controlled settings can increase blood pressure, heart rate, 
      and body temperature. Previous studies indicate thatO-demethylated metabolites of 
      MDMA contribute to its adverse effects. As such, limiting the conversion of MDMA 
      to reactive metabolites may mitigate some of its adverse effects and potentially 
      improve its safety profile for therapeutic use. METHODS: We compared the 
      interoceptive and hyperthermic effects of a deuterium-substituted form of MDMA 
      (d2-MDMA) to MDMA using rodent drug discrimination and biotelemetry procedures, 
      respectively. RESULTS: Compared to MDMA, d2-MDMA produced full substitution for a 
      1.5 mg/kg MDMA training stimulus with equal potency and effectiveness in the drug 
      discrimination experiment. In addition, d2-MDMA produced increases in body 
      temperature that were shorter-lasting and of lower magnitude compared to 
      equivalent doses of MDMA. Last, d2-MDMA and MDMA were equally effective in 
      reversing the hypothermic effects of the selective 5-HT(2A/2C) antagonist 
      ketanserin. CONCLUSION: These findings indicate that deuterium substitution of 
      hydrogen at the methylenedioxy ring moiety does not impact MDMA's interoceptive 
      effects, and compared to MDMA, d2-MDMA has less potential for producing 
      hyperthermic effects and likely has similar pharmacodynamic properties. Given 
      that d2-MDMA produces less adverse effects than MDMA, but retains similar 
      desirable effects that are thought to relate to the effective treatment of PTSD, 
      additional investigations into its effects on cardiovascular functioning and 
      pharmacokinetic properties are warranted.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Berquist, Michael D
AU  - Berquist MD
AD  - Department of Pharmacology and Toxicology, College of Medicine, University of 
      Arkansas for Medical Sciences, 4301 W. Markham #611, Little Rock, AR, 72205, USA.
FAU - Leth-Petersen, Sebastian
AU  - Leth-Petersen S
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Universitetsparken 2, 2100 Kobenhavn O, 
      Denmark.
FAU - Kristensen, Jesper Langgaard
AU  - Kristensen JL
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Universitetsparken 2, 2100 Kobenhavn O, 
      Denmark.
FAU - Fantegrossi, William E
AU  - Fantegrossi WE
AD  - Department of Pharmacology and Toxicology, College of Medicine, University of 
      Arkansas for Medical Sciences, 4301 W. Markham #611, Little Rock, AR, 72205, USA. 
      Electronic address: WEFantegrossi@uams.edu.
LA  - eng
GR  - HHSF223201310079C/FD/FDA HHS/United States
GR  - T32 DA022981/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200113
PL  - Ireland
TA  - Drug Alcohol Depend
JT  - Drug and alcohol dependence
JID - 7513587
RN  - 0 (Serotonin Agents)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Body Temperature Regulation/*drug effects/physiology
MH  - Conditioning, Operant/*drug effects/physiology
MH  - Discrimination Learning/*drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*analogs & derivatives/*pharmacology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rodentia
MH  - Serotonin Agents/chemistry/pharmacology
MH  - Telemetry/*methods
OTO - NOTNLM
OT  - 3,4-Methylenedioxymethamphetamine
OT  - Biotelemetry
OT  - Deuterated MDMA
OT  - Drug discrimination
OT  - Ketanserin
OT  - MDMA
OT  - d2-MDMA
COIS- Declaration of Competing Interest No conflict declared.
EDAT- 2020/01/20 06:00
MHDA- 2021/01/20 06:00
CRDT- 2020/01/20 06:00
PHST- 2019/11/07 00:00 [received]
PHST- 2020/01/07 00:00 [revised]
PHST- 2020/01/08 00:00 [accepted]
PHST- 2020/01/20 06:00 [pubmed]
PHST- 2021/01/20 06:00 [medline]
PHST- 2020/01/20 06:00 [entrez]
AID - S0376-8716(20)30015-6 [pii]
AID - 10.1016/j.drugalcdep.2020.107850 [doi]
PST - ppublish
SO  - Drug Alcohol Depend. 2020 Mar 1;208:107850. doi: 
      10.1016/j.drugalcdep.2020.107850. Epub 2020 Jan 13.