Ultralong-lasting nerve block: triethyldodecyl ammonium bromide is probably a neurotoxin rather than a local anesthetic.
The profile and duration of action of triethyldodecyl ammonium bromide (TEA-C12) on natural spike activity of rabbit aortic nerve was examined. To study the profile of action, a segment of the aortic nerve of anesthetized rabbits was placed in a perfusion chamber and exposed to increasing concentrations of TEA-C12 and, for comparison, of procaine. Total nerve activity was recorded continuously and its change related to drug concentrations (concentration/effect curves). The half-lives of onset time after drug administration and recovery following drug-washout were also determined. To study the duration of conduction block induced by TEA-C12, the aortic nerve of anesthetized rabbits was exposed to a concentration slightly higher than the minimal blocking concentration for an average time of 130 min after complete conduction block occurred. Three to 40 days later, the nerves were examined both neurophysiologically and neuropathologically. TEA-C12 blocked nerve activity in a concentration-related manner, as did procaine; however, the onset time (t1/2) was much slower for TEA-C12 (9.2 min) than for procaine (2.2 min). Most importantly, TEA-C12 block could not be reversed within 9 h of drug-washout, whereas all the procaine-blocked nerves completely recovered (t1/2 = 3.0 min). Nerve activity was completely blocked by TEA-C12 and nerve block was accompanied by severe morphological damage with complete loss of myelinated nerve fibers and severe axonal edema of the remaining axons for about 4 weeks. Nerve function completely recovered, but with only partial morphological restoration between day 30 and 40 after the initial block.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Experimental Anesthesiology, University of Duesseldorf, Germany.
P
P
Lipfert
R J
RJ
Seitz
J O
JO
Arndt
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local; D000818:Animals; D001011:Aorta / Q000294:innervation; D009407:Nerve Block; D009498:Neurotoxins; D010525:Peripheral Nerves / Q000187:drug effects / Q000648:ultrastructure; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors
D000779:Anesthetics, Local; D009498:Neurotoxins; D000644:Quaternary Ammonium Compounds; C054210:N,N,N-triethyl-1-dodecylammonium