抗胆碱酯酶对心脏烟碱样反应的阻断作用。

Blockade of cardiac nicotinic responses by anticholinesterases.

Paddle B M, Dowling M H

Department of Defence, DSTO, Aeronautical and Maritime Research Laboratory, Melbourne VIC, Australia.

Gen Pharmacol. 1996 Jul;27(5):861-72. doi: 10.1016/0306-3623(95)02107-8.

Abstract

Tacrine (10 microM) and physostigmine (10 microM) completely inhibited the positive chronotropic and inotropic actions of acetylcholine (ACh) or nicotine in the atropinized guinea pig right atria. 2. Edrophonium (6 microM) and soman (0.1 microM) completely inhibited these nicotinic responses, as well as the associated increase in pyridine nucleotide fluorescence and vasodilation induced by ACh in the atropinized guinea pig perfused heart. 3. The 200-fold increase in noradrenaline release induced by ACh in the perfused heart was blocked by 10 microM tacrine and 6 microM edrophonium. 4. Tacrine (10 microM) significantly (16-32%) reduced the basal heart rate of both preparations. 5. Edrophonium (6 microM) induced a five- to sixfold increase in basal 3,4-dihydroxyphenyl-(ethylene) glycol (DOPEG) release. 6. The inhibition of nicotinic receptor activation in the atria by the anticholinesterases appears mainly non-competitive. IC50 values range from 0.1 to 10 microM in the perfused heart to 1 to 100 microM in atria (in either case tacrine about 2 microM). 7. The possibility that these compounds have a direct action at nicotinic receptors is discussed.

摘要

他克林（10微摩尔）和毒扁豆碱（10微摩尔）完全抑制了阿托品化豚鼠右心房中乙酰胆碱（ACh）或尼古丁的正性变时和变力作用。2. 依酚氯铵（6微摩尔）和梭曼（0.1微摩尔）完全抑制了这些烟碱样反应，以及阿托品化豚鼠灌注心脏中由ACh诱导的吡啶核苷酸荧光增加和血管舒张。3. 灌注心脏中由ACh诱导的去甲肾上腺素释放增加200倍被10微摩尔他克林和6微摩尔依酚氯铵阻断。4. 他克林（10微摩尔）显著降低了两种制剂的基础心率（16 - 32%）。5. 依酚氯铵（6微摩尔）使基础3,4 - 二羟基苯乙二醇（DOPEG）释放增加了五到六倍。6. 抗胆碱酯酶对心房烟碱受体激活的抑制作用似乎主要是非竞争性的。在灌注心脏中IC50值范围为0.1至10微摩尔，在心房中为1至100微摩尔（在任何一种情况下他克林约为2微摩尔）。7. 讨论了这些化合物在烟碱受体上具有直接作用的可能性。