Tetrodotoxin for prolonged local anesthesia with minimal myotoxicity

  title={Tetrodotoxin for prolonged local anesthesia with minimal myotoxicity},
  author={Robert F. Padera and Julie Y Tse and Evangelia Bellas and Daniel S. Kohane},
  journal={Muscle \& Nerve},
Conventional local anesthetics such as bupivacaine cause considerable myotoxicity and neurotoxicity, whereas tetrodotoxin (TTX) does not. Tetrodotoxin combined with bupivacaine or vasoconstrictors produces long‐duration nerve blockade. To assess whether these prolonged blocks can be produced without increased myotoxicity, Sprague‐Dawley rats were injected with bupivacaine, TTX, and both, or TTX plus epinephrine. Median durations of thermal nociceptive blockade were, respectively, 188, 401, 882… 

Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia, and sciatic nerve histology was benign for all groups.

Prolonged Duration Local Anesthesia by Combined Delivery of Capsaicin- and Tetrodotoxin-Loaded Liposomes.

Capsaicin may be useful for its synergistic effects on other formulations even when used in very small, safe quantities and did not cause detectable local or systemic toxicity.

Effect of chemical permeation enhancers on nerve blockade.

It is demonstrated that CPEs can provide marked prolongation of nerve blockade from TTX but not bupivacaine, without apparent local tissue toxicity, which may enhance the clinical applicability of TTX for prolonged-duration local anesthesia.

Tetrodotoxin, Epinephrine, and Chemical Permeation Enhancer Combinations in Peripheral Nerve Blockade

CPEs can prolong the duration of nerve blockade across a range of concentrations of TTX and could also be used to reduce the concentration of epinephrine needed to achieve a given degree of nerve block, which may be useful in enhancing nerve blockade from site 1 sodium channel blockers.

Local Neurotoxicity and Myotoxicity Evaluation of Cyclodextrin Complexes of Bupivacaine and Ropivacaine

Evaluating the local neural and muscular toxicity of these new formulations containing 0.5% BVC or RVC complexed with HP-&bgr;-CD found that they presented a lower myotoxicity and a similar cytotoxic effect when compared to plain local anesthetic solutions.

Duration and Local Toxicity of Sciatic Nerve Blockade With Coinjected Site 1 Sodium-Channel Blockers and Quaternary Lidocaine Derivatives

Coadministration of site 1 sodium-channel blockers and QLDs greatly prolongs the duration of peripheral nerve block without enhancing local tissue injury, but minimal myotoxicity still persists.

Local Toxicity from Local Anesthetic Polymeric Microparticles

Lidocaine and bupivacaine PLGA microspheres resulted in similar degrees of myotoxicity, irrespective of drug loading, and Caution is warranted in the use of such devices near muscle and nerve.

Local Myotoxicity from Sustained Release of Bupivacaine from Microparticles

Whereas the release vehicles themselves were not myotoxic, both burst and extended release of bupivacaine were, and a possible implication is that myotoxicity is an inevitable concomitant of sustained release of local anesthetics.



A Re‐examination of Tetrodotoxin for Prolonged Duration Local Anesthesia

Combinations of epinephrine or bupivacaine with tetrodotoxin or with other high‐potency toxins active on sodium channels should be examined for the potential to provide clinical useful, prolonged nerve blockade.

Tissue Injury from Tricyclic Antidepressants Used as Local Anesthetics

TCAs do not appear to offer any advantages over conventional local anesthetics and do appear to risk substantially increased toxicity, although some animals receiving large concentrations of amitriptyline developed spontaneous recrudescence of nerve blockade or had irreversible nerve blockade, both of which may reflect nerve injury.

The Local Anesthetic Properties and Toxicity of Saxitonin Homologues for Rat Sciatic Nerve Block In Vivo

Compared to those with neosaxitoxin, decarbamoyl saxitoxin, and tetrodotoxin, the potency of TTX was intermediate between those of the saxitoxins, and its therapeutic index was slightly better, while that ofTTX is slightly better.

Myotoxicity of Local Anesthetics and Regeneration of the Damaged Muscle Fibers

With all anesthetics, the initial damage to and breakdown of muscle fibers was restored by regeneration and 30-day muscles showed relatively few long-term effects of the damage.

Local Myotoxicity of Bupivacaine in Rabbits After Continuous Supraclavicular Brachial Plexus Block

Background and Objectives. Local anesthetics including bupivacaine have been known to be myotoxic. Continuous brachial plexus blocks with bupivacaine provide good postoperative pain relief, but their

The Local Anesthetic Activity of Tetrodotoxin Alone and in Combination With Vasoconstrictors and Local Anesthetics

The studies present some indirect evidence that local anesthetics enhance TTX activity by reversibly increasing the permeability of various neural barriers to TTX.

Sciatic Nerve Blockade in Infant, Adolescent, and Adult Rats: , A Comparison of Ropivacaine with Bupivacaine

For a given absolute dose, sciatic blockade in infant rats lasts longer than in adolescents or adults, and the doses causing toxicity were much higher in infants than in adults, so this probably does not correspond to a wider therapeutic index.

Local Anesthetic Neurotoxicity Does Not Result from Blockade of Voltage-Gated Sodium Channels

Results indicate that local anesthetic neurotoxicity does not result from blockade of the sodium channel, and suggest that development of a safer anesthetic is a realistic goal.