BRADYCARDIA PRODUCED BY PYRIDOSTIGMINE AND PHYSOSTIGMINE

Purpose: 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 rec orded, Erythrocyte cholinesterase activity of arterial blood was measu red using a radiometric technique, Nicotinic and muscarinic M-1 recept ors were blocked with hexamethonium and pirenzepine, respectively. M-2 receptors were blocked with gallamine, pancuronium and AFDX-116. Resu lts: With pyridostigmine and physostigmine, the dose-response relation ship 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 act ivity 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 p yridostigmine and physostigmine was blocked by hexamethonium (ED50 10 +/- 1.3 and 15.3 +/- 2.4 mg.kg(-1), respectively), pirenzepine (ED50 6 8 +/- 16 and 138 +/- 32 mu g.k(-1), respectively), gallamine (56 +/- 1 1 and 67 +/- 17 mu g.kg(-1), respectively), pancuronium (32 +/- 10 and 30 +/- 4 mu g.kg(-1), respectively), and AFDX-116 (31 +/- 4 and 28 +/ - 4 mu g.kg(-1), respectively). Conclusion: The bradycardia produced b y reversible anticholinesterase drugs containing a carbamyl group is n ot clearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscarinic M-1 and high sensitivity to muscarinic M-2 receptor antagonists.