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ID 31502
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Author
Abstract

Vecuronium is hydrolyzed in the body to 3-deacetyl (ORG 7268), 17-deacetyl (ORG NC58), and 3, 17-bis-deacetyl (ORG 7402) derivatives. Interactions of vecuronium and these metabolites were studied in phrenic nerve-hemidiaphragm preparations of rats. As already reported, ORG 7268 had a potent neuromuscular blocking action, and ORG NC58 and ORG 7402 had a weak neuromuscular blocking action. As expected, ORG 7268 increased the degree of neuromuscular block by vecuronium. However, a low concentration (10 microM) of ORG NC58 and ORG 7402 reversed the block by vecuronium. At a high concentration (50 microM), ORG NC58 and ORG 7402 increased the degree of block by vecuronium. Although we do not have enough data to explain these paradoxical reversal of neuromuscular block at this moment, we postulate that these results reflect the interaction between "slow" and "fast" competitive antagonists. Regardless of the mechanism, it should be emphasized that the concentrations of ORG NC58 and ORG 7402 which are necessary to reverse the block are much lower than those which facilitate the block. It is conceivable that this paradoxical reversal of the block occurs in experimental and clinical situations. Therefore, in determining the neuromuscular blocking action of a compound, the "antagonistic" effect of its metabolites should also be considered.

Keywords
vecuronium
neuromuscular trasmission
drug interaction
competitive inhibition
muscle relaxant
Amo Type
Article
Published Date
1985-12
Publication Title
Acta Medica Okayama
Volume
volume39
Issue
issue6
Publisher
Okayama University Medical School
Start Page
471
End Page
480
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
File Version
publisher
Refereed
True
PubMed ID
Web of Sience KeyUT