Post-junctional interactions between neuromuscular blocking agents and ethanol at the mouse neuromuscular junction.
OBJECTIVE
Ethanol is known to have both pre-synaptic and post-synaptic effects at a range of loci in the mammalian nervous system, including the neuromuscular junction. However, the effects of ethanol on evoked synaptic transmission have not been previously studied at the mouse neuromuscular junction. Here, we report on the effects of ethanol on evoked neuromuscular transmission and the interaction of ethanol with non-depolarizing blocking drugs.


METHODS
Electrophysiological techniques to measure synaptic potentials and synaptic currents were employed in this study.


RESULTS
Ethanol (≥100 mM) produced increases in the amplitudes of both spontaneous and evoked synaptic events. Under conditions in which neuromuscular transmission was blocked by (+)-tubocurarine, ethanol (12-100 mM) produced greater increases in evoked response amplitude than in spontaneous response amplitude recorded in the absence of (+)-tubocurarine. Ethanol (100 mM) did not affect evoked neurotransmitter release in low-calcium/high-magnesium solutions. With respect to the clinically used neuromuscular blocking drugs, ethanol (100 mM) interfered with the blocking action of vecuronium, but not cisatracurium.


CONCLUSIONS
Under these conditions, the stimulant effect of ethanol on neuromuscular transmission is exclusively on the post-junctional elements, both to enhance transmission through nicotinic receptors and also via interactions with neuromuscular blocking agents. These actions of ethanol on neuromuscular transmission may affect the dosage of neuromuscular blockers required in patients who have imbibed significant amounts of alcohol.
Searl
T J
TJ
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL, USA. tjs026@northwestern.edu
Silinsky
E M
EM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D055366:Synaptic Potentials / Q000187:drug effects*; D014403:Tubocurarine / Q000494:pharmacology
D009466:Neuromuscular Blocking Agents; D000431:Ethanol; D014403:Tubocurarine