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.