Document Detail


Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats.
MedLine Citation:
PMID:  20105175     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 microM) 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 microM) 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.
Authors:
Y Zhang; M Guzinski; E I Eger; M J Laster; M Sharma; R A Harris; H C Hemmings
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-01-25
Journal Detail:
Title:  British journal of pharmacology     Volume:  159     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-07-09     Revised Date:  2013-09-13    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  872-8     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Fuwai Hospital and Cardiovascular Institute, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Administration, Inhalation
Anesthetics, Inhalation / administration & dosage*
Animals
Dose-Response Relationship, Drug
Drug Interactions
Immobilization
Infusions, Parenteral
Isoflurane / administration & dosage*
Male
Motor Activity / drug effects*
Pain Threshold / drug effects*
Rats
Rats, Long-Evans
Sodium Channel Blockers / administration & dosage*
Sodium Channels / drug effects*,  metabolism
Tetrodotoxin / administration & dosage*
Veratridine / administration & dosage*
Grant Support
ID/Acronym/Agency:
1P01GM47818/GM/NIGMS NIH HHS; GM58055/GM/NIGMS NIH HHS; P01 GM047818-150004/GM/NIGMS NIH HHS; R01 AA006399/AA/NIAAA NIH HHS; R01 AA006399-28/AA/NIAAA NIH HHS; R01 GM058055/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Sodium Channel Blockers; 0/Sodium Channels; 26675-46-7/Isoflurane; 4368-28-9/Tetrodotoxin; 71-62-5/Veratridine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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