| Abstrakt: |
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 recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. Nicotinic and muscarinic M1receptors were blocked with hexamethonium and pirenzepine, respectively. M2receptors were blocked with gallamine, pancuronium and AFDX-116. Results: With pyridostigmine and physostigmine, the dose-response relationship for the decrease in heart rate (ED501.05 ± 0.25 and 0.198 ± 0.03 mg·kg−1, respectively) was shifted to the right of that for the inhibition of cholinesterase activity (ED500.094 ± 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 pyndostigmine and physostigmine was blocked by hexamethonium (ED5010 ± 1.3 and 15.3 ± 2.4 mg·kg−1, respectively), pirenzepine (ED5068 ± 16 and 138 ± 32 μg·kg−1. respectively), gallamine (56 ± 11 and 67 ± 17 μg·kg−1, respectively ), pancuronium (32 ± 10 and 30 ± 4 μg·kg−1, respectively), and AFDX-116 (31 ± 4 and 28 ± 4 μg·kg−1, respectively). Conclusion: The bradycardia produced by reversible anticholinesterase drugs containing a carbamyl group is not dearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscannic M1and a high sensitivity to muscarinic M2receptor antagonists. |
Full text from SpringerLink