title: Pralidoxime inhibits paraoxon-induced depression of rocuronium-neuromuscular block in a time-dependent fashion.
abstract: OBJECTIVE
  The composite effects of organophosphorus (OP)-cholinesterase (ChE) inhibitors and oximes on the actions of nondepolarizing neuromuscular blockers in acute OP-ChE inhibitor intoxication have not been evaluated in detail. We investigated the effects of paraoxon (Pox) (an OP-ChE inhibitor) and pralidoxime (PAM) (an oxime) on the nondepolarizing neuromuscular blocking action of rocuronium.
  
  
  METHODS
  Isometric twitch tensions of rat left phrenic nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Analysis of variance with post hoc testing was used for statistical comparison, and P < .05 was accepted as significant.
  
  
  RESULTS
  Rocuronium reduced the indirectly elicited twitch tensions in normal (50% inhibitory concentration [IC(50)], 9.84 [9.64-10.04] μM, mean [95% confidence interval]) and all pretreated diaphragms (P < .01, n = 6) in a concentration-dependent fashion. Paraoxon caused a rightward shift in the rocuronium concentration-twitch tension curve (IC(50), 15.48 [15.24-15.72] μM). The rightward shift was completely inhibited by previous copretreatment (IC(50), 9.98 [9.77-10.20] μM) and partially inhibited by simultaneous copretreatment (IC(50), 11.68 [11.45-11.91] μM) with PAM but was not inhibited by subsequent copretreatment (IC(50), 13.69 [13.39-13.99] μM) with PAM (P < .01, n = 6). Atropine did not influence the rightward shift (P < .01, n = 6).
  
  
  CONCLUSIONS
  Paraoxon depressed rocuronium-induced neuromuscular block by inhibiting ChEs, and the action of Pox was inhibited by PAM. Pralidoxime acts more intensely when applied earlier. The time-dependent effect of PAM indicates that the preceding presence of PAM in proximity to ChEs before Pox is necessary for definite suppression of the Pox-induced ChE inhibition.
authors.affiliation: Department of Traumatology and Critical Care Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. enarimat@sapmed.ac.jp
authors.forename: Eichi
authors.initials: E
authors.lastname: Narimatsu
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Niiya
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Yamakage
mesh_terms: D000732:Androstanols / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010261:Paraoxon / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077123:Rocuronium; D013997:Time Factors
chemical_list: D000732:Androstanols; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D003473:Neuromuscular Nondepolarizing Agents; D011220:Pralidoxime Compounds; C028797:pralidoxime; D010261:Paraoxon; D000077123:Rocuronium