Effects of presynaptic muscarinic cholinoreceptor blockade on neuromuscular transmission as assessed by the train-of-four and the tetanic fade response to rocuronium

This study investigated the effect of muscarinic M-1 and M-2 receptor antagonists on the rocuronium-induced train of four (TOF) fade and tetanic fade, respectively. Ex-vivo phrenic nerves and diaphragms were obtained from adult Sprague-Dawley rats and stabilized in Krebs buffer; the nerve-stimulated muscle TOF fade was observed at 20s intervals. For the TOF study, phrenic nerves and diaphragms were incubated with pirenzepine (an M-1 blocker) at concentrations of 0nmolL(-1) (control), 10nmolL(-1) (PZP10), or 100nmolL(-1) (PZP100). Rocuronium was then administered incrementally until the first twitch tension had depressed by >95% during TOF stimulation. The mean TOF ratios were compared when the first twitch tensions were depressed by 40%-50%. For the tetanic fade study, 50Hz/5s tetani was applied initially, 30min after the administration of a loading dose of rocuronium and methoctramine (an M-2 receptor blocker, loaded at 0molL(-1) [control], 1molL(-1) [MET1], or 10molL(-1) [MET10]). The EC95 of rocuronium was significantly lower in the PZP10 group than in the control group. In the PZP10 group, the TOF ratios at 50% and first twitch tension depression were significantly lower than those in the control group (P=.02). During tetanic stimulation, the tetanic fade was significantly enhanced in the MET10 group compared to the other groups. This study shows that antagonists of muscarinic M-1 and M-2 receptors affect the rocuronium-induced neuromuscular block as demonstrated by the reduced EC95 and TOF ratios (M-1 antagonist, pirenzepine) or the enhanced 50-Hz tetanic fade (M-2 antagonist, methoctramine).