Traditional local anesthetics, like lidocaine, bupivacaine, and tetracaine, produce neural blockade by binding deep within the central pore of the transmembrane sodium channel. Local anesthetics have a limited duration of action and their use is restricted by cardiac and central nervous system toxicity. In contrast, marine toxins like tetrodotoxin and the saxitoxins bind at a distinct location on the sodium channel and have varying affinities for cardiac sodium channels. In this issue of Anesthesiology, Cravero, Berde and their colleagues show that when neosaxitoxin and bupivacaine are administered concomitantly, a prolonged-duration sensory block is created without evidence of added cardiac or central nervous system toxicity, demonstrating the potential for prolonged, but reversible, neural blockade.

  • Lobo et al.: A Phase 1, Dose-escalation, Double-blind, Block-randomized, Controlled Trial of Safety and Efficacy of Neosaxitoxin Alone and in Combination with 0.2% Bupivacaine, with and without Epinephrine, for Cutaneous Anesthesia, p. 873

  • Templin et al.: Neosaxitoxin in Rat Sciatic Block: Improved Therapeutic Index Using Combinations with Bupivacaine, with and without Epinephrine, p. 886

  • Lahaye and Butterworth: Site-1 Sodium Channel Blockers as Local Anesthetics: Will Neosaxitoxin Supplant the Need for Continuous Nerve Blocks?, p. 741