Stein R D, Backman S B, Collier B, Polosa C
Department of Anaesthesia, Royal Victoria Hospital, Montreal, Quebec, Canada.
Can J Anaesth. 1997 Dec;44(12):1286-92. doi: 10.1007/BF03012778.
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.
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.
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).
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.
根据吡啶斯的明和毒扁豆碱与胆碱酯酶抑制作用的关系以及对胆碱能受体拮抗剂阻断作用的敏感性，研究它们在急性心脏去神经支配动物模型中所产生的心动过缓。
对猫进行麻醉、切断迷走神经并给予普萘洛尔治疗。持续记录心率。采用放射测量技术测定动脉血红细胞胆碱酯酶活性。分别用六甲铵和哌仑西平阻断烟碱样受体和毒蕈碱样M1受体。用加拉明、泮库溴铵和AFDX - 116阻断M2受体。
使用吡啶斯的明和毒扁豆碱时，心率降低的剂量 - 反应关系（ED50分别为1.05±0.25和0.198±0.03mg·kg-1）相对于胆碱酯酶活性抑制的剂量 - 反应关系（ED50分别为0.094±0.03和0.032±0.01mg·kg-1）向右偏移。胆碱酯酶活性的降低在累积剂量分别为0.56±0.08和0.32±0.08mg·kg-1时达到平台期。相比之下，心动过缓效应似乎没有平台期。吡啶斯的明和毒扁豆碱所产生的心动过缓被六甲铵（ED50分别为10±1.3和15.3±2.4mg·kg-1）、哌仑西平（ED50分别为68±16和138±32μg·kg-1）、加拉明（分别为56±11和67±17μg·kg-1）、泮库溴铵（分别为32±10和30±4μg·kg-1）以及AFDX - 116（分别为31±4和28±- 4μg·kg-1）阻断。
含氨甲酰基的可逆性抗胆碱酯酶药物所产生的心动过缓与胆碱酯酶活性程度无明显关联，对烟碱样受体和毒蕈碱样M1受体敏感性低，对毒蕈碱样M2受体拮抗剂敏感性高。
