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Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats
Author(s) -
Zhang Y,
Guzinski M,
Eger II EI,
Laster MJ,
Sharma M,
Harris RA,
Hemmings Jr HC
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00583.x
Subject(s) - veratridine , tetrodotoxin , potency , pharmacology , isoflurane , sodium channel , anesthesia , medicine , chemistry , sodium channel blocker , sodium , endocrinology , in vitro , biochemistry , organic chemistry
Background and purpose: Results from several studies point to voltage‐gated Na + channels as potential mediators of the immobility produced by inhaled anaesthetics. We hypothesized that the intrathecal administration of tetrodotoxin, a drug that blocks Na + channels, should enhance anaesthetic potency, and that concurrent administration of veratridine, a drug that augments Na + channel opening, should reverse the increase in potency. Experimental approach: We measured the change in isoflurane potency for reducing movement in response to a painful stimulus as defined by MAC (minimum alveolar concentration of anaesthetic required to abolish movement in 50% of subjects) caused by intrathecal infusion of various concentrations of tetrodotoxin into the lumbothoracic subarachnoid space of rats, and the change in MAC caused by the administration of a fixed dose of tetrodotoxin plus various doses of intrathecal veratridine. Key results: Intrathecal infusion of tetrodotoxin (0.078–0.63 µM) produced a reversible dose‐related decrease in MAC, of more than 50% at the highest concentration. Intrathecal co‐administration of veratridine (1.6–6.4 µM) reversed this decrease in a dose‐related manner, with nearly complete reversal at the highest veratridine dose tested. Conclusions and implications: Intrathecal administration of tetrodotoxin increases isoflurane potency (decreases isoflurane MAC), and intrathecal administration of veratridine counteracts this effect in vivo . These findings are consistent with a role for voltage‐gated Na + channel blockade in the immobility produced by inhaled anaesthetics.