PMID- 24328722
OWN - NLM
STAT- MEDLINE
DCOM- 20140819
LR  - 20211021
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 171
IP  - 1
DP  - 2014 Jan
TI  - Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on 
      cardiovascular function in conscious rats.
PG  - 83-91
LID - 10.1111/bph.12423 [doi]
AB  - BACKGROUND AND PURPOSE: The cardiovascular effects produced by 
      3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') contribute to its acute 
      toxicity, but the potential role of its metabolites in these cardiovascular 
      effects is not known. Here we examined the effects of MDMA metabolites on 
      cardiovascular function in rats. EXPERIMENTAL APPROACH: Radiotelemetry was 
      employed to evaluate the effects of s.c. administration of racemic MDMA and its 
      phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious 
      male rats. KEY RESULTS: MDMA (1-20 mg.kg(-1)) produced dose-related increases in 
      BP, HR and activity. The peak effects on HR occurred at a lower dose than peak 
      effects on BP or activity. The N-demethylated metabolite, 
      3,4-methylenedioxyamphetamine (MDA), produced effects that mimicked those of 
      MDMA. The metabolite 3,4-dihydroxymethamphetamine (HHMA; 1-10 mg.kg(-1)) 
      increased HR more potently and to a greater extent than MDMA, whereas 
      3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. 
      Neither dihydroxy metabolite altered motor activity. The metabolites 
      4-hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine 
      (HMA) did not affect any of the parameters measured. The tachycardia produced by 
      MDMA and HHMA was blocked by the beta-adrenoceptor antagonist propranolol. 
      CONCLUSIONS AND IMPLICATIONS: Our results demonstrate that HHMA may contribute 
      significantly to the cardiovascular effects of MDMA in vivo. As such, determining 
      the molecular mechanism of action of HHMA and the other hydroxyl metabolites of 
      MDMA warrants further study.
CI  - Published 2013. This article is a U.S. Government work and is in the public 
      domain in the USA.
FAU - Schindler, Charles W
AU  - Schindler CW
AD  - Preclinical Pharmacology, National Institutes of Health, National Institute on 
      Drug Abuse, Intramural Research Program, Baltimore, MD, USA.
FAU - Thorndike, Eric B
AU  - Thorndike EB
FAU - Blough, Bruce E
AU  - Blough BE
FAU - Tella, Srihari R
AU  - Tella SR
FAU - Goldberg, Steven R
AU  - Goldberg SR
FAU - Baumann, Michael H
AU  - Baumann MH
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Hallucinogens)
RN  - 117652-28-5 (4-hydroxy-3-methoxymethamphetamine)
RN  - 13026-44-3 (3-O-methyl-alpha-methyldopamine)
RN  - 15398-87-5 (alpha-methylepinine)
RN  - 44RAL3456C (Methamphetamine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R7339QLN1C (Deoxyepinephrine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/metabolism/pharmacology
MH  - Adrenergic beta-Antagonists/pharmacology
MH  - Animals
MH  - Blood Pressure/*drug effects
MH  - Cardiovascular System/*drug effects
MH  - Consciousness
MH  - Deoxyepinephrine/analogs & derivatives/metabolism/pharmacology
MH  - Dopamine/analogs & derivatives/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Hallucinogens/metabolism/*pharmacology
MH  - Heart Rate/*drug effects
MH  - Male
MH  - Metabolic Detoxication, Phase I
MH  - Methamphetamine/analogs & derivatives/metabolism/pharmacology
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/metabolism/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Telemetry
MH  - Time Factors
PMC - PMC3874698
OTO - NOTNLM
OT  - BP
OT  - MDMA metabolites
OT  - heart rate
OT  - noradrenergic
OT  - telemetry
EDAT- 2013/12/18 06:00
MHDA- 2014/08/20 06:00
PMCR- 2015/01/01
CRDT- 2013/12/17 06:00
PHST- 2013/03/25 00:00 [received]
PHST- 2013/07/22 00:00 [revised]
PHST- 2013/09/05 00:00 [accepted]
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/08/20 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 10.1111/bph.12423 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2014 Jan;171(1):83-91. doi: 10.1111/bph.12423.