PREJUNCTIONAL ACTION OF NEOSTIGMINE ON MOUSE NEUROMUSCULAR PREPARATIONS

被引:14
作者
BRAGA, MFM
ROWAN, EG
HARVEY, AL
BOWMAN, WC
机构
[1] UNIV STRATHCLYDE, DEPT PHYSIOL & PHARMACOL, GLASGOW G1 1XW, SCOTLAND
[2] UNIV STRATHCLYDE, STRATHCLYDE INST DRUG RES, GLASGOW G1 1XW, SCOTLAND
关键词
ANTAGONISTS; NEOSTIGMINE; NEUROMUSCULAR FUNCTION; ACETYLCHOLINE RELEASE;
D O I
10.1093/bja/70.4.405
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
We have studied the effects of neostigmine on the mouse diaphragm and triangularis sterni isolated nerve-muscle preparations. Mechanical responses of the muscle, end-plate potentials and miniature end-plate potentials, and extracellularly recorded nerve ending currents were recorded. In the mouse diaphragm nerve-muscle preparations, neostigmine 1 mumol litre-1 continued to produce some antagonism of tubocurarine-induced block after cholinesterase had been inactivated completely by diisopropyl fluorophosphate 22 mumol litre-1. In the mouse triangularis sterni preparation, neostigmine 0.1-1 mumol litre-1 increased the quantal content of the end-plate potential in a concentration-dependent manner. This effect appeared to be sufficient to account for the cholinesterase-independent antagonistic action to tubocurarine under the conditions of the experiments. Neostigmine 1-100 mumol litre-1 depressed the amplitude of the K+ currents of the perineural waveforms in a concentration-dependent manner, and this may account for its ability to increase the quantal content of the end-plate potential. Although inhibition of acetylcholinesterase is the main mechanism of action of neostigmine, the drug also exerts an additional direct action on motor nerve endings to block the delayed rectifier K+ channels and enhance transmitter release. This effect occurred at clinically relevant concentrations of neostigmine. Physostigmine and pyridostigmine did not possess this additional action.
引用
收藏
页码:405 / 410
页数:6
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