title: Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Tian-Sheng Memorial Hospital, Tong-Kang, Pintong, Taiwan.
authors: Tzu-Rong
authors: TR
authors: Su
authors: Yu-Shiang
authors: YS
authors: Hung
authors: Shiang Suo
authors: SS
authors: Huang
authors: Hsing Hui
authors: HH
authors: Su
authors: Ching-Chyuan
authors: CC
authors: Su
authors: George
authors: G
authors: Hsiao
authors: Yi-Hung
authors: YH
authors: Chen
authors: Min-Jon
authors: MJ
authors: Lin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000494:pharmacology*; D001667:Binding, Competitive; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D019148:Neuromuscular Blockade / Q000379:methods*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000378:metabolism; D013498:Suramin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D014403:Tubocurarine / Q000494:pharmacology*
chemical_list: C110258:4,4,',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis(benzene-1,3-disulfonate); D001557:Benzenesulfonates; D003473:Neuromuscular Nondepolarizing Agents; D011978:Receptors, Nicotinic; D013498:Suramin; D000109:Acetylcholine; D014403:Tubocurarine