title: Glycopyrrolate intensifies neuromuscular blockade produced by atracurium in the rat diaphragm preparation.
abstract: The effect of glycopyrrolate (Glycopyrronium, a muscarinic antagonist) (10 mumol.litre-1) and neostigmine (1 mumol.litre-1) on atracurium (0.1-100 mumol.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 mumol.litre-1 (atracurium +glycopyrrolate +neostigmine) (means +/- SEM, n = 6, P less than 0.001, with respect to control value of atracurium alone). 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.
authors.affiliation: Anaesthetics Unit, London Hospital Medical College, Whitechapel, England.
authors.forename: F A
authors.initials: FA
authors.lastname: Wali
authors.forename: C H
authors.initials: CH
authors.lastname: Dark
authors.forename: A
authors.initials: A
authors.lastname: Altinel
authors.forename: C J
authors.initials: CJ
authors.lastname: Jones
mesh_terms: D000818:Animals; D001279:Atracurium / Q000494:pharmacology*; D006024:Glycopyrrolate / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009388:Neostigmine / Q000494:pharmacology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012132:Respiratory Muscles / Q000187:drug effects*
chemical_list: D009466:Neuromuscular Blocking Agents; D011759:Pyrrolidines; D001279:Atracurium; D009388:Neostigmine; D006024:Glycopyrrolate