Ephedrine blocks rat sciatic nerve in vivo and sodium channels in vitro.
BACKGROUND
The sympathomimetic drug ephedrine has been used intrathecally as the sole local anesthetic for labor and delivery. Because ephedrine may be a useful adjuvant to local anesthetics, the authors investigated the local anesthetic properties of ephedrine in a rat sciatic nerve block model and the underlying mechanism in cultured cells stably expressing Na channels.


METHODS
After approval of the animal protocol, the sciatic nerves of anesthetized rats were exposed by lateral incision of the thighs, 0.2 ml ephedrine at 0.25, 1, 2.5, or 5% and/or bupivacaine at 0.125% was injected, and the wound was closed. Motor and sensory/nociceptive functions were evaluated by the force achieved by pushing against a balance and the reaction to pinch, respectively. The whole cell configuration of the patch clamp technique was used to record Na currents from human embryonal kidney cells stably transfected with Nav1.4 channels.


RESULTS
The nociception blockade was significantly longer than the motor blockade at test doses of 2.5 and 5% of ephedrine, or when 1% ephedrine was combined with 0.125% bupivacaine (analysis of variance with repeated measures, P < 0.001, n = 8/group). In vitro, the 50% inhibitory concentrations of ephedrine at -150 and -60 mV were 1,043 +/- 70 and 473 +/- 13 mum, respectively. High-frequency stimulation revealed a use-dependent block of 18%, similar to most local anesthetics.


CONCLUSIONS
Because ephedrine's properties are at least partly due to Na channel blockade, detailed histopathologic investigations are justified to determine the potential of ephedrine as an adjuvant to clinically used local anesthetics.
Hung
Yu-Chun
YC
Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan.
Kau
Yi-Chuan
YC
Zizza
Anthony M
AM
Edrich
Thomas
T
Zurakowski
David
D
Myers
Robert R
RR
Wang
Ging Kuo
GK
Gerner
Peter
P
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004809:Ephedrine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007267:Injections; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects; D009407:Nerve Block; D009475:Neurons, Afferent / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects*; D026941:Sodium Channel Blockers
D000316:Adrenergic alpha-Agonists; D026941:Sodium Channel Blockers; D004809:Ephedrine