The local anesthetic activity of tetrodotoxin alone and in combination with vasoconstrictors and local anesthetics.

Tetrodotoxin (TTX), alone and in combination with various vasoconstrictors and local anesthetics, was evaluated for its ability to produce peripheral nerve blocks in the rat and central neural blocks in the cat and dog. High frequency and long duration of block can be attained if sufficiently high concentrations of TTX are used, although latency is long and high dosage may produce systemic toxicity. Frequency and mean duration of block can be increased and systemic toxicity reduced if TTX is administered with a vasoconstrictive agent. Conventional local anesthetics also enhance the nerve-blocking activity of TTX. When appropriate concentrations of TTX and local anesthetics are used, a high frequency of blocks characterized by short latency and long duration can be demonstrated. The studies present some indirect evidence that local anesthetics enhance TTX activity by reversibly increasing the permeability of various neural barriers to TTX.