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 language | English |
|---|---|
| Pages (from-to) | 1039-1046 |
| Number of pages | 8 |
| Journal | Life Sciences |
| Volume | 88 |
| Issue number | 23-24 |
| DOIs | |
| Publication status | Published - Jun 6 2011 |
Fingerprint
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
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 journal › Article
}
TY - JOUR
T1 - Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine
AU - Su, Tzu Rong
AU - Hung, Yu Shiang
AU - Huang, Shiang Suo
AU - Su, Hsing Hui
AU - Su, Ching Chyuan
AU - Hsiao, George
AU - Chen, Yi Hung
AU - Lin, Min Jon
PY - 2011/6/6
Y1 - 2011/6/6
N2 - 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.
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.
KW - D-tubocurarine
KW - Neuromuscular blockade reversal agents
KW - NF449
KW - Nicotinic acetylcholine receptor
KW - Purinoceptors
KW - Suramin analogues
UR - http://www.scopus.com/inward/record.url?scp=79957555014&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957555014&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2011.03.013
DO - 10.1016/j.lfs.2011.03.013
M3 - Article
C2 - 21453711
AN - SCOPUS:79957555014
VL - 88
SP - 1039
EP - 1046
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 23-24
ER -