Neosaxitoxin as a local anesthetic: preliminary observations from a first human trial.
BACKGROUND
Neosaxitoxin is a phycotoxin that reversibly blocks the voltage-gated sodium channels at the neuronal level. Its activity results in blocking the axonal conduction, stopping the propagation of the nerve impulse. The objective of the present work was to evaluate neosaxitoxin as a local anesthetic in a human trial.


METHODS
The authors conducted a randomized, double-blind, placebo-controlled trial with 10 healthy volunteers. Subcutaneous injections were made in the middle posterior skin of the calf: one leg received 50 microg neosaxitoxin, and the contra-lateral leg received placebo. The anesthetic effect was evaluated using a standardized human sensory and pain model. TSA II Neurosensory Analyzer (Medoc Ltd, Minneapolis, MN) and von Frey technique were used to evaluate five parameters: sensory threshold for warm and cold, pain thresholds for heat and cold, and mechanical touch perception threshold. Measurements were made 0, 1, 3, 6, 9, 12, 16, 24, and 48 h after the injections.


RESULTS
For all the patients, effective and complete blocking of the evaluated parameters was obtained. As the blocking began to revert gradually, heat pain was the first to return to normal values after 3 h. Cold pain was the longest sensation abolished, achieving 24 h of blockade. The toxin was undetected in blood and urine samples. No adverse reactions to neosaxitoxin were detected.


CONCLUSIONS
Neosaxitoxin showed an effective local anesthetic effect when injected in the subcutaneous plane. The efficacy of a 50-microg dose of neosaxitoxin was shown. This is the first report of neosaxitoxin as a local anesthetic in a human trial.
Rodriguez-Navarro
Alberto J
AJ
Hospital Clínico Universidad de Chile and Hospital Padre Hurtado, and Research Affiliate, Laboratorio Bioquímica de Membrana, Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad de Chile, Santiago, Chile. alrodrigu@med.uchile.cl
Lagos
Nestor
N
Lagos
Marcelo
M
Braghetto
Italo
I
Csendes
Attila
A
Hamilton
James
J
Figueroa
Cristian
C
Truan
Dominique
D
Garcia
Carlos
C
Rojas
Andres
A
Iglesias
Veronica
V
Brunet
Luis
L
Alvarez
Francisco
F
D000293:Adolescent; D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D012530:Saxitoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology*
D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D012530:Saxitoxin; C034902:neosaxitoxin