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  • Title: [The local anesthetic effect of tetrodotoxin on the natural spike activity of the depressor nerve in rabbits].
    Author: Lipfert P, Beyer G, Lömm M.
    Journal: Reg Anaesth; 1989 Jul; 12(4):69-75. PubMed ID: 2772276.
    Abstract:
    Tetrodotoxin (TTX) has been presented as an ultra-long-acting local anesthetic. Because its duration of action on myelinated nerve fibers of warm-blooded animals is unknown the effect of TTX on natural spike activity (A-delta fibers) of rabbit aortic nerve in vivo was studied. In 13 animals, a segment of the aortic nerve was placed in a perfusion chamber and exposed to increasing concentrations of TTX (n = 8) and, for comparison, of procaine (n = 8), which like TTX has a high pka. Total nerve activity and its change as related to drug concentrations was recorded continuously (concentration effect curves). The half-lives (t1/2) of onset time after drug administration and recovery following drug washout were also determined. TTX blocked nerve activity in a concentration-related manner, as did procaine; however, the potency of TTX (EC50 = 3.3 +/- 0.8.10(-9), cm = 1.3 +/- 0.4.10(-8) mol/l) was about 50,000 times higher than that of procaine (EC50 = 1.6 +/- 0.2.10(-4), cm = 2.5 4/- 0.3.10(-4) mol/l). Onset time did not differ statistically (p = 0.08) between TTX (t1/2 = 3.5 +/- 0.4 min) and procaine (t1/2 = 2.2 +/- 0.5 min). Most importantly, TTX block could not be reversed within 1-5 h of drug washout (n = 5) or was reversed incompletely (13%, 66%, and 90% of control activity) with t1/2 16 to 21 min. In contrast, all the procaine-blocked nerves recovered completely (t1/2 = 3.0 +/- 0.4 min). TTX blocks myelinated A-delta fibers of warm-blooded animals with lower concentrations and for a longer time than nonmyelinated fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
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