Experimental study of tetrodotoxin, a long-acting topical anesthetic.
OBJECTIVE
To determine the effectiveness and toxicity of tetrodotoxin for use as a long-acting topical anesthetic.


METHODS
Four groups of six rabbits each received a 40-microl aliquot of either tetrodotoxin in one of three concentrations (10 mM, 1 mM, or 0.1 mM) or proparacaine 0.5% into the inferior conjunctival cul-de-sac of one eye, with the fellow eye of each rabbit receiving 40 microl of a 60-mM, pH 4.3 sodium citrate vehicle as a control. Corneal sensation was tested for up to 8 hours after administration of drugs, and response was noted by no blink, partial blink without full eyelid closure, and full blink. Slit-lamp examination at 12 and 24 hours after administration and pachymetry before and 24 hours after administration were performed to detect corneal toxicity.


RESULTS
Rabbits receiving all three concentrations of tetrodotoxin did not demonstrate any ocular irritation, corneal thickening, or signs of systemic toxicity. At a dose of 10 mM, tetrodotoxin produced an anesthetic effect lasting up to 8 hours. At 1 mM, tetrodotoxin was an effective but shorter-acting anesthetic. At 0.1 mM, tetrodotoxin had no significant anesthetic effect. Proparacaine-treated rabbits initially were anesthetic, but this effect was largely gone by 1 hour and completely gone by 3 hours.


CONCLUSIONS
Tetrodotoxin is a long-acting topical anesthetic in the rabbit cornea. Although additional toxicity studies are required, tetrodotoxin may provide an effective, long-lasting topical anesthetic for use in pain control after corneal procedures such as photorefractive keratectomy.
Schwartz
D M
DM
Department of Ophthalmology, University of California San Francisco Medical Center, USA. schwartz@sirius.com
Fields
H L
HL
Duncan
K G
KG
Duncan
J L
JL
Jones
M R
MR
D000772:Anesthesia, Local / Q000379:methods*; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001767:Blinking / Q000187:drug effects; D003315:Cornea / Q000187:drug effects* / Q000502:physiology; D009883:Ophthalmic Solutions; D011430:Propoxycaine / Q000008:administration & dosage; D011817:Rabbits; D012449:Safety; D012677:Sensation / Q000187:drug effects; D013779:Tetrodotoxin / Q000008:administration & dosage* / Q000633:toxicity
D000779:Anesthetics, Local; D009883:Ophthalmic Solutions; D013779:Tetrodotoxin; C005717:proxymetacaine; D011430:Propoxycaine