MDMA activates skeletal muscle nicotinic acetylcholine receptors.

[BilZ0r]

J Pharmacol Exp Ther. 2005 Jun 9

3,4-methylenedioxymethamphetamine (MDMA, ecstasy) activates skeletal muscle nicotinic acetylcholine receptors.

Klingler W, Heffron JJ, Jurkat-Rott K, Osullivan G, Alt A, Schlesinger F, Bufler J, Lehmann-Horn F.

Ulm University, Departments of Anesthesiology and Applied Physiology.

Adverse MDMA 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 SR 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 (alphaBgt), 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.

This one excited me straight away, because I've recently become more and more interested in MDMAs excitatory effect of facial muscles. I though we might have had some kind of answer in this paper, maybe a combination of serotonins excitatory action of facial muscles [1] and now, if it excites nicotinic receptors then that explains a lot.

However, there is one problem, these guys wouldn't know a dose-response curve if it bit them in the ass. They only test MDMA over a range on 100-1000µM, concentrations WAY above even MDMA's paltry 5-HT2A receptor affinity... this paper is completely pointless. The effect seems so weak it's hard to comment on... the PDSP has give MDMA nearly the full treatment and MDMAs affinity for any of the nicotinic receptors they look at is way about there 10µM threashold. Don't waste your time reading this paper.

 

[botaanik]

That's intersting. My nicotine usage is rised on mdma, now I know why OK keep us posted Bilz0r about that subject.

 

[BilZ0r]

^ Maybe, but I doubt it. That's probably because of the fact that MDMA will make smoking seem smoother (it's an anti-tussive i.e. it stops you coughing) and because it activates dopaminergic systems, which increase reinstatement of drug taking behaviour.