| Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats. | |
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MedLine Citation:
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PMID: 20105175 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Y Zhang; M Guzinski; E I Eger; M J Laster; M Sharma; R A Harris; H C Hemmings |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-01-25 |
Journal Detail:
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Title: British journal of pharmacology Volume: 159 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-04-14 Completed Date: 2010-07-09 Revised Date: 2013-03-01 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 872-8 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, Fuwai Hospital and Cardiovascular Institute, Beijing, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
| Chemical | |
Reg. No./Substance:
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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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