title: Bradycardia produced by pyridostigmine and physostigmine.
abstract: OBJECTIVE
  The bradycardia produced by pyridostigmine and physostigmine in an animal model of acute cardiac denervation was examined according to its relation to cholinesterase inhibition and sensitivity to block by cholinergic receptor antagonists.
  
  
  METHODS
  Cats were anaesthetised, vagotomised and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. Nicotinic and muscarinic M1 receptors were blocked with hexamethonium and pirenzepine, respectively. M2 receptors were blocked with gallamine, pancuronium and AFDX-116.
  
  
  RESULTS
  With pyridostigmine and physostigmine the dose-response relationship for the decrease in heart rate (ED50 1.05 +/- 0.25 and 0.198 +/- 0.03 mg.kg-1, respectively) was shifted to the right of that for the inhibition of cholinesterase activity (ED50 0.094 +/- 0.03 and 0.032 +/- 0.01 mg.kg-1, respectively). The decrease in cholinesterase activity reached a plateau at a cumulative dose of 0.56 +/- 0.08 and 0.32 +/- 0.08 mg.kg-1, respectively. In contrast, there did not appear to be a plateau in the bradycardic effect. The bradycardia produced by pyridostigmine and physostigmine was blocked by hexamethonium (ED50 10 +/- 1.3 and 15.3 +/- 2.4 mg.kg-1, respectively), pirenzepine (ED50 68 +/- 16 and 138 +/- 32 micrograms.kg-1, respectively), gallamine (56 +/- 11 and 67 +/- 17 micrograms.kg-1, respectively), pancuronium (32 +/- 10 and 30 +/- 4 micrograms.kg-1, respectively), and AFDX-116 (31 +/- 4 and 28 +/- 4 micrograms.kg-1, respectively).
  
  
  CONCLUSIONS
  The bradycardia produced by reversible anticholinesterase drugs containing a carbamyl group is not clearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscarinic M1 and a high sensitivity to muscarinic M2 receptor antagonists.
authors.affiliation: Department of Anaesthesia, Royal Victoria Hospital, Montreal, Quebec, Canada.
authors.forename: R D
authors.initials: RD
authors.lastname: Stein
authors.forename: S B
authors.initials: SB
authors.lastname: Backman
authors.forename: B
authors.initials: B
authors.lastname: Collier
authors.forename: C
authors.initials: C
authors.lastname: Polosa
mesh_terms: D000818:Animals; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D002415:Cats; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006339:Heart Rate / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010830:Physostigmine / Q000633:toxicity*; D011729:Pyridostigmine Bromide / Q000633:toxicity*; D014628:Vagotomy
chemical_list: D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D010830:Physostigmine; D002802:Cholinesterases; D011729:Pyridostigmine Bromide