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Summary  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 20 s intervals. For the  TOF  study, phrenic nerves and diaphragms were incubated with pirenzepine (an M 1  blocker) at concentrations of 0 nmol L −1  (control), 10 nmol L −1  ( PZP 10), or 100 nmol L −1  ( PZP 100). 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, 50 Hz/5 s tetani was applied initially, 30 min after the administration of a loading dose of rocuronium and methoctramine (an M 2  receptor blocker, loaded at 0 μmol L −1  [control], 1 μmol L −1  [ MET 1], or 10 μmol L −1  [ MET 10]). The  EC  95  of rocuronium was significantly lower in the  PZP 10 group than in the control group. In the  PZP 10 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  MET 10 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  EC  95  and  TOF  ratios (M 1  antagonist, pirenzepine) or the enhanced 50‐Hz tetanic fade (M 2  antagonist, methoctramine).

clinical and experimental pharmacology and physiology

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