Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine

Tzu Rong Su, Yu Shiang Hung, Shiang Suo Huang, Hsing Hui Su, Ching Chyuan Su, George Hsiao, Yi Hung Chen, Min Jon Lin

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Abstract

Aims: The aim of this study was to investigate the mechanism for the reversal effect of NF449 (a suramin analogue) on the neuromuscular block induced by d-tubocurarine (d-TC). Main methods: Nerve-stimulated muscle contractions and end-plate potentials were performed in mouse phrenic nerve-diaphragm preparations. Acetylcholine (ACh)-induced muscle contractions were performed in the chick biventer cervicis preparations. Presynaptic nerve terminal waveform recordings were performed in mouse triangularis sterni preparations. Key findings: Amongst the suramin analogues in this study, only the NF449 and suramin were able to reverse the blockade effect produced by d-TC on nerve-stimulated muscle contractions. Each of these suramin analogues (NF007, NF023, NF279 and NF449) alone has no significant effect on the amplitude of nerve-stimulated muscle contractions. NF449 and suramin also showed the antagonising effects on the inhibition of end-plate potentials induced by d-TC. Furthermore, pre-treatment with NF449 can antagonise the inhibition of d-TC in ACh-induced contractions of chick biventer cervicis muscle. NF449 produced a greater rightward shift of the dose-response inhibition curve for d-TC than did suramin. Because other purinergic 2X (P2X) receptor antagonists, NF023 and NF279, do not have the reverse effects on the neuromuscular blockade of d-TC, the effect of NF449 seems irrelevant to inhibition of P2X receptors. Significance: These data suggest that NF449 was able to compete with the binding of d-TC on the nicotinic ACh receptors, and the effect of NF449 was more potent than suramin in reducing the inhibition of d-TC. The structure of NF449 may provide useful information for designing potent antidotes against neuromuscular toxins.

Original languageEnglish
Pages (from-to)1039-1046
Number of pages8
JournalLife Sciences
Volume88
Issue number23-24
DOIs
Publication statusPublished - Jun 6 2011

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Keywords

  • D-tubocurarine
  • Neuromuscular blockade reversal agents
  • NF449
  • Nicotinic acetylcholine receptor
  • Purinoceptors
  • Suramin analogues

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Su, T. R., Hung, Y. S., Huang, S. S., Su, H. H., Su, C. C., Hsiao, G., Chen, Y. H., & Lin, M. J. (2011). Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine. Life Sciences, 88(23-24), 1039-1046. https://doi.org/10.1016/j.lfs.2011.03.013