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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

Tubocurarine
Neuromuscular Blockade
Suramin
Muscle
Muscle Contraction
Excitatory Postsynaptic Potentials
Acetylcholine
Purinergic Antagonists
4,4,',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis(benzene-1,3-disulfonate)
Purinergic Receptors
Antidotes
Phrenic Nerve
Presynaptic Terminals
Nicotinic Receptors
Diaphragms
Diaphragm

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., ... 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

Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine. / Su, Tzu Rong; Hung, Yu Shiang; Huang, Shiang Suo; Su, Hsing Hui; Su, Ching Chyuan; Hsiao, George; Chen, Yi Hung; Lin, Min Jon.

In: Life Sciences, Vol. 88, No. 23-24, 06.06.2011, p. 1039-1046.

Research output: Contribution to journalArticle

Su, TR, Hung, YS, Huang, SS, Su, HH, Su, CC, Hsiao, G, Chen, YH & Lin, MJ 2011, 'Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine', Life Sciences, vol. 88, no. 23-24, pp. 1039-1046. https://doi.org/10.1016/j.lfs.2011.03.013
Su, Tzu Rong ; Hung, Yu Shiang ; Huang, Shiang Suo ; Su, Hsing Hui ; Su, Ching Chyuan ; Hsiao, George ; Chen, Yi Hung ; Lin, Min Jon. / Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine. In: Life Sciences. 2011 ; Vol. 88, No. 23-24. pp. 1039-1046.
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AB - 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.

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