Block of the endplate acetylcholine receptor channel by the sympathomimetic agents ephedrine, pseudoephedrine, and albuterol.
Recent observations suggest that some patients with congenital myasthenic syndromes respond favorably to ephedrine, pseudoephedrine, or albuterol. Conventional microelectrode studies, however, provide no clear explanation for a beneficial effect of ephedrine in endplate diseases. To gain further insight into how these drugs affect neuromuscular transmission, we investigated their effects on the kinetic properties of the acetylcholine (ACh) receptor. Single channel currents were recorded from rat lumbrical muscles endplates using low concentrations of ACh and 2.5-100 microM of drugs. Between 10-100 microM, each drug progressively increased the rate of channel closure in a concentration dependent manner, consistent with an open-channel block. Albuterol acted as a sequential fast-acting channel blocker, increasing the mean burst duration in a concentration dependent manner without altering the total open time per burst or the duration of intraburst blockages. Increasing concentrations of ephedrine and pseudoephedrine also increased the number of intraburst closures but decreased the total open time per burst. None of the drugs altered single channel conductance. The channel blocking effects of ephedrine and pseudoephedrine might reduce the synaptic overactivity that occurs in the slow-channel myasthenic syndromes or in endplate ACh esterase deficiency, but these effects occur at concentrations not attainable in clinical practice.
Milone
M
M
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
Engel
A G
AG
D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004809:Ephedrine / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects*; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects*
D007473:Ion Channels; D011950:Receptors, Cholinergic; D004809:Ephedrine; D000420:Albuterol