Glycopyrrolate intensifies neuromuscular blockade produced by atracurium in the rat diaphragm preparation

Abstract The effect of glycopyrrolate (Glycopyrronium, a muscarinic antagonist) (10 μmol.litre −1 ) and neostigmine (1 μmol.litre −1 ) on atracurium (0.1–100 μmol.litre −1 ) - induced neuromuscular blockade was studied in the rat isolated phrenic nerve-diaphragm preparation, to see if glycopyrrolate intensified the neuromuscular blockade produced by atracurium in this preparation. Atracurium had a rapid onset of blockade, reaching a complete block in 30–40 s. Glycopyrrolate had no significant effect on indirectly-elicited twitch (0.2 Hz) tension, whereas it significantly increased atracurium-induced depression of twitch tension and shortened the time needed to a complete block by 10 s. Combinations of glycopyrrolate+ neostigmine, only slightly reversed atracurium-induced blockade, if compared to the reversal by neostigmine alone. The mean concentrations to produce 50% depression of twitch tension were: 1.6±0.1 (atracurium), 0.3±0.1 atracurium +glycopyrrolate), 4.8±0.2 (atracurium +neostigmine) and 2.7±0.1 μmol. litre −1 (atracurium +glycopyrrolate +neostigmine) (means±SEM, n=6, P It was concluded that glycopyrrolate enhanced atracurium-induced neuromuscular blockade in the rat diaphragm preparation, and that this effect should be noted when dosing glycopyrrolate in man.