PMID- 15947037
OWN - NLM
STAT- MEDLINE
DCOM- 20051021
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 314
IP  - 3
DP  - 2005 Sep
TI  - 3,4-Methylenedioxymethamphetamine (ecstasy) activates skeletal muscle nicotinic 
      acetylcholine receptors.
PG  - 1267-73
AB  - Adverse 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) effects are usually 
      ascribed to neurotransmitter release in the central nervous system. Since 
      clinical features such as fasciculations, muscle cramps, rapidly progressing 
      hyperthermia, hyperkalemia, and rhabdomyolysis point to the skeletal muscle as 
      additional target, we studied the effects of MDMA on native and cultured skeletal 
      muscle. We addressed the question whether malignant hyperthermia (MH)-susceptible 
      (MHS) muscle is predisposed to adverse MDMA reactions. Force measurements on 
      muscle strips showed that 100 microM MDMA, a concentration close to that 
      determined in some MDMA users, regularly enhanced the sensitivity of skeletal 
      muscle to caffeine-induced contractures but did not cause contractures on its 
      own. The left-shift of the dose-response curve induced by MDMA was greater in 
      normal than in MHS muscle. Furthermore, MDMA did not release Ca(2+) from isolated 
      sarcoplasmic reticulum vesicles. These findings do not support the view of an 
      MH-triggering effect on muscle. However, MDMA induced Ca(2+) transients in 
      myotubes and increased their acidification rate. Surprisingly, 
      alpha-bungarotoxin, a specific antagonist of the nicotinic acetylcholine receptor 
      (nAChR), abolished these MDMA effects. The nAChR agonistic action of MDMA was 
      confirmed by patch-clamp measurements of ion currents on human embryonic kidney 
      cells expressing nAChR. We conclude that the neuromuscular junction is a target 
      of MDMA and that an activation of nAChR contributes to the muscle-related 
      symptoms of MDMA users. The drug may be of particular risk in individuals with 
      abundant extrajunctional nAChR such as in generalized denervation or muscle 
      regeneration processes and may act on central nAChR.
FAU - Klingler, Werner
AU  - Klingler W
AD  - Department of Anesthesiology, Ulm University, Germany.
FAU - Heffron, James J A
AU  - Heffron JJ
FAU - Jurkat-Rott, Karin
AU  - Jurkat-Rott K
FAU - O'sullivan, Grainne
AU  - O'sullivan G
FAU - Alt, Andreas
AU  - Alt A
FAU - Schlesinger, Friedrich
AU  - Schlesinger F
FAU - Bufler, Johannes
AU  - Bufler J
FAU - Lehmann-Horn, Frank
AU  - Lehmann-Horn F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050609
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Receptors, Nicotinic)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Malignant Hyperthermia/metabolism
MH  - Muscle Contraction/drug effects
MH  - Muscle Fibers, Skeletal/drug effects
MH  - Muscle, Skeletal/*drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*adverse effects
MH  - Rats
MH  - Receptors, Nicotinic/*drug effects
MH  - Sarcoplasmic Reticulum/drug effects/metabolism
EDAT- 2005/06/11 09:00
MHDA- 2005/10/22 09:00
CRDT- 2005/06/11 09:00
PHST- 2005/06/11 09:00 [pubmed]
PHST- 2005/10/22 09:00 [medline]
PHST- 2005/06/11 09:00 [entrez]
AID - jpet.105.086629 [pii]
AID - 10.1124/jpet.105.086629 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2005 Sep;314(3):1267-73. doi: 10.1124/jpet.105.086629. Epub 
      2005 Jun 9.